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Article ; Online: Tumor-specific T-cell memory: clearing the regulatory T-cell hurdle.

Côté, Anik L / Usherwood, Edward J / Turk, Mary Jo

2008 Volume 68, Issue 6, Page(s) 1614–1617

Abstract: Antitumor immune responses can be stimulated by interfering with regulatory T-cell (T(reg)) function. However, this effect is short lived unless T-cell memory to tumor antigens can be generated. Our recent studies show that T(reg) cells not only limit ... ...

Abstract	Antitumor immune responses can be stimulated by interfering with regulatory T-cell (T(reg)) function. However, this effect is short lived unless T-cell memory to tumor antigens can be generated. Our recent studies show that T(reg) cells not only limit primary responses to tumor/self-antigens in tumor-bearing hosts but also prevent the natural generation of T-cell memory to such antigens. Here, we discuss the role of T(reg) cells in suppressing T-cell memory after surgical excision of tumors and the potential clinical benefits of overcoming this suppression.
MeSH term(s)	Animals ; Antigens, Neoplasm/immunology ; Humans ; Immunologic Memory ; Melanoma, Experimental/immunology ; Melanoma, Experimental/pathology ; Melanoma, Experimental/surgery ; Mice ; Neoplasms/immunology ; Neoplasms/pathology ; Neoplasms/surgery ; T-Lymphocytes, Regulatory/immunology
Chemical Substances	Antigens, Neoplasm
Language	English
Publishing date	2008-03-13
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	1432-1
ISSN	1538-7445 ; 0008-5472
ISSN (online)	1538-7445
ISSN	0008-5472
DOI	10.1158/0008-5472.CAN-07-6012
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Article ; Online: CXCR4 and matrix metalloproteinase-1 are elevated in breast carcinoma-associated fibroblasts and in normal mammary fibroblasts exposed to factors secreted by breast cancer cells.

Eck, Sarah M / Côté, Anik L / Winkelman, William D / Brinckerhoff, Constance E

Molecular cancer research : MCR

2009 Volume 7, Issue 7, Page(s) 1033–1044

Abstract: The complex molecular communications that occur between neoplastic and stromal cells within the tumor microenvironment play an integral role in breast cancer pathogenesis. Carcinoma-associated fibroblasts (CAF) produce tumor-enhancing factors and have ... ...

Abstract	The complex molecular communications that occur between neoplastic and stromal cells within the tumor microenvironment play an integral role in breast cancer pathogenesis. Carcinoma-associated fibroblasts (CAF) produce tumor-enhancing factors and have been strongly implicated in breast cancer development. Similar to the way in which tumors have been compared with "wounds that never heal," CAFs have been equated to activated fibroblasts, which are present in inflammatory environments, in which they aid in wound healing through tissue remodeling and repair. Matrix metalloproteinase-1 (MMP-1) and G protein-coupled receptor, CXCR4, are elevated in these activated fibroblasts, in which they facilitate angiogenesis and matrix degradation, processes that are also vital to breast cancer metastasis. In this study, we investigated MMP-1 and CXCR4 expression in normal human mammary fibroblasts (HMF) exposed to soluble breast cancer factors. Historically, elevated CXCR4 expression is associated with breast cancer cells. However, we show that soluble factors secreted by SUM102 breast cancer cells stimulated the expression of MMP-1 and CXCR4 in HMFs. As a result, these stromal cells acquired an invasive and migratory phenotype. To confirm the clinical relevancy of our findings, we analyzed CAFs obtained from primary breast cancers. These cells also displayed elevated MMP-1 and CXCR4 levels compared with counterpart fibroblasts, and were more invasive and migratory. Together, our data suggest that soluble breast cancer factors initiate the transdifferentiation of normal HMFs to tumor-promoting CAFs, and that through the induction of MMP-1 and CXCR4 levels, these cells exhibit an invasive and migratory phenotype.
MeSH term(s)	Animals ; Breast/cytology ; Breast/enzymology ; Breast/metabolism ; Breast Neoplasms/genetics ; Breast Neoplasms/metabolism ; Breast Neoplasms/pathology ; Cell Growth Processes/physiology ; Cell Movement/physiology ; Collagen Type I/metabolism ; Female ; Fibroblasts/drug effects ; Fibroblasts/enzymology ; Fibroblasts/metabolism ; Fibroblasts/pathology ; Gene Expression ; Humans ; Intercellular Signaling Peptides and Proteins/metabolism ; Intercellular Signaling Peptides and Proteins/pharmacology ; Interleukin-8/metabolism ; Matrix Metalloproteinase 1/biosynthesis ; Matrix Metalloproteinase 1/genetics ; Matrix Metalloproteinase 1/metabolism ; Mice ; RNA, Messenger/biosynthesis ; RNA, Messenger/genetics ; Receptors, CXCR4/biosynthesis ; Receptors, CXCR4/genetics ; Receptors, CXCR4/metabolism ; Signal Transduction
Chemical Substances	CXCR4 protein, human ; CXCR4 protein, mouse ; Collagen Type I ; Intercellular Signaling Peptides and Proteins ; Interleukin-8 ; RNA, Messenger ; Receptors, CXCR4 ; Matrix Metalloproteinase 1 (EC 3.4.24.7)
Language	English
Publishing date	2009-07-07
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2098788-2
ISSN	1557-3125 ; 1541-7786
ISSN (online)	1557-3125
ISSN	1541-7786
DOI	10.1158/1541-7786.MCR-09-0015
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Article ; Online: Protective CD8 memory T cell responses to mouse melanoma are generated in the absence of CD4 T cell help.

Côté, Anik L / Byrne, Katelyn T / Steinberg, Shannon M / Zhang, Peisheng / Turk, Mary Jo

PloS one

2011 Volume 6, Issue 10, Page(s) e26491

Abstract: Background: We have previously demonstrated that temporary depletion of CD4 T cells in mice with progressive B16 melanoma, followed by surgical tumor excision, induces protective memory CD8 T cell responses to melanoma/melanocyte antigens. We also ... ...

Abstract	Background: We have previously demonstrated that temporary depletion of CD4 T cells in mice with progressive B16 melanoma, followed by surgical tumor excision, induces protective memory CD8 T cell responses to melanoma/melanocyte antigens. We also showed that persistence of these CD8 T cells is supported, in an antigen-dependent fashion, by concurrent autoimmune melanocyte destruction. Herein we explore the requirement of CD4 T cell help in priming and maintaining this protective CD8 T cell response to melanoma. Methodology and principal findings: To induce melanoma/melanocyte antigen-specific CD8 T cells, B16 tumor bearing mice were depleted of regulatory T cells (T(reg)) by either temporary, or long-term continuous treatment with anti-CD4 (mAb clone GK1.5). Total depletion of CD4 T cells led to significant priming of IFN-γ-producing CD8 T cell responses to TRP-2 and gp100. Surprisingly, treatment with anti-CD25 (mAb clone PC61), to specifically deplete T(reg) cells while leaving help intact, was ineffective at priming CD8 T cells. Thirty to sixty days after primary tumors were surgically excised, mice completely lacking CD4 T cell help developed autoimmune vitiligo, and maintained antigen-specific memory CD8 T cell responses that were highly effective at producing cytokines (IFN-γ, TNF-α, and IL-2). Mice lacking total CD4 T cell help also mounted protection against re-challenge with B16 melanoma sixty days after primary tumor excision. Conclusions and significance: This work establishes that CD4 T cell help is dispensable for the generation of protective memory T cell responses to melanoma. Our findings support further use of CD4 T cell depletion therapy for inducing long-lived immunity to cancer.
MeSH term(s)	Animals ; Antigen Presentation ; CD4-Positive T-Lymphocytes/immunology ; CD8-Positive T-Lymphocytes/immunology ; Cytokines/biosynthesis ; Immunologic Memory/immunology ; Melanoma, Experimental/immunology ; Mice ; T-Lymphocytes/immunology
Chemical Substances	Cytokines
Language	English
Publishing date	2011-10-26
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0026491
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Protective CD8 memory T cell responses to mouse melanoma are generated in the absence of CD4 T cell help.

Anik L Côté / Katelyn T Byrne / Shannon M Steinberg / Peisheng Zhang / Mary Jo Turk

PLoS ONE, Vol 6, Iss 10, p e

2011 Volume 26491

Abstract: We have previously demonstrated that temporary depletion of CD4 T cells in mice with progressive B16 melanoma, followed by surgical tumor excision, induces protective memory CD8 T cell responses to melanoma/melanocyte antigens. We also showed that ... ...

Abstract	We have previously demonstrated that temporary depletion of CD4 T cells in mice with progressive B16 melanoma, followed by surgical tumor excision, induces protective memory CD8 T cell responses to melanoma/melanocyte antigens. We also showed that persistence of these CD8 T cells is supported, in an antigen-dependent fashion, by concurrent autoimmune melanocyte destruction. Herein we explore the requirement of CD4 T cell help in priming and maintaining this protective CD8 T cell response to melanoma.To induce melanoma/melanocyte antigen-specific CD8 T cells, B16 tumor bearing mice were depleted of regulatory T cells (T(reg)) by either temporary, or long-term continuous treatment with anti-CD4 (mAb clone GK1.5). Total depletion of CD4 T cells led to significant priming of IFN-γ-producing CD8 T cell responses to TRP-2 and gp100. Surprisingly, treatment with anti-CD25 (mAb clone PC61), to specifically deplete T(reg) cells while leaving help intact, was ineffective at priming CD8 T cells. Thirty to sixty days after primary tumors were surgically excised, mice completely lacking CD4 T cell help developed autoimmune vitiligo, and maintained antigen-specific memory CD8 T cell responses that were highly effective at producing cytokines (IFN-γ, TNF-α, and IL-2). Mice lacking total CD4 T cell help also mounted protection against re-challenge with B16 melanoma sixty days after primary tumor excision.This work establishes that CD4 T cell help is dispensable for the generation of protective memory T cell responses to melanoma. Our findings support further use of CD4 T cell depletion therapy for inducing long-lived immunity to cancer.
Keywords	Medicine ; R ; Science ; Q
Subject code	570
Language	English
Publishing date	2011-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Talking about treatment benefits, harms, and what matters to patients in radiation oncology: an observational study.

Pilote, Laurie / Côté, Luc / Chipenda Dansokho, Selma / Brouillard, Émilie / Giguère, Anik M C / Légaré, France / Grad, Roland / Witteman, Holly O

BMC medical informatics and decision making

2019 Volume 19, Issue 1, Page(s) 84

Abstract: Background: Shared decision making is associated with improved patient outcomes in radiation oncology. Our study aimed to capture how shared decision-making practices-namely, communicating potential harms and benefits and discussing what matters to ... ...

Abstract	Background: Shared decision making is associated with improved patient outcomes in radiation oncology. Our study aimed to capture how shared decision-making practices-namely, communicating potential harms and benefits and discussing what matters to patients-occur in usual care. Methods: We invited a convenience sample of clinicians and patients in a radiation oncology clinic to participate in a mixed methods study. Prior to consultations, clinicians and patients completed self-administered questionnaires. We audio-recorded consultations and conducted qualitative content analysis. Patients completed a questionnaire immediately post-consultation about their recall and perceptions. Results: 11 radiation oncologists, 4 residents, 14 nurses, and 40 patients (55% men; mean age 64, standard deviation or SD 9) participated. Patients had a variety of cancers; 30% had been referred for palliative radiotherapy. During consultations (mean length 45 min, SD 16), clinicians presented a median of 8 potential harms (interquartile range 6-11), using quantitative estimates 17% of the time. Patients recalled significantly fewer harms (median recall 2, interquartile range 0-3, t(38) = 9.3, p < .001). Better recall was associated with discussing potential harms with a nurse after seeing the physician (odds ratio 7.5, 95% confidence interval 1.3-67.0, p = .04.) Clinicians initiated 63% of discussions of harms and benefits while patients and families initiated 69% of discussions about values and preferences (Chi-squared(1) = 37.8, p < .001). 56% of patients reported their clinician asked what mattered to them. Conclusions: Radiation oncology clinics may wish to use interprofessional care and initiate more discussions about what matters to patients to heed Jain's (2014) reminder that, "a patient isn't a disease with a body attached but a life into which a disease has intruded."
MeSH term(s)	Adult ; Aged ; Decision Making, Shared ; Female ; Humans ; Male ; Middle Aged ; Patient Preference ; Physician-Patient Relations ; Radiation Oncology ; Referral and Consultation ; Research Design ; Surveys and Questionnaires
Language	English
Publishing date	2019-04-11
Publishing country	England
Document type	Journal Article ; Observational Study ; Research Support, Non-U.S. Gov't
ISSN	1472-6947
ISSN (online)	1472-6947
DOI	10.1186/s12911-019-0800-5
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Article ; Online: User-centered and theory-based design of a professional training program on shared decision-making with older adults living with neurocognitive disorders: a mixed-methods study.

Lawani, Moulikatou Adouni / Turgeon, Yves / Côté, Luc / Légaré, France / Witteman, Holly O / Morin, Michèle / Kroger, Edeltraut / Voyer, Philippe / Rodriguez, Charo / Giguere, Anik

BMC medical informatics and decision making

2021 Volume 21, Issue 1, Page(s) 59

Abstract: Background: We know little about the best approaches to design training for healthcare professionals. We thus studied how user-centered and theory-based design contribute to the development of a distance learning program for professionals, to increase ... ...

Abstract	Background: We know little about the best approaches to design training for healthcare professionals. We thus studied how user-centered and theory-based design contribute to the development of a distance learning program for professionals, to increase their shared decision-making (SDM) with older adults living with neurocognitive disorders and their caregivers. Methods: In this mixed-methods study, healthcare professionals who worked in family medicine clinics and homecare services evaluated a training program in a user-centered approach with several iterative phases of quantitative and qualitative evaluation, each followed by modifications. The program comprised an e-learning activity and five evidence summaries. A subsample assessed the e-learning activity during semi-structured think-aloud sessions. A second subsample assessed the evidence summaries they received by email. All participants completed a theory-based questionnaire to assess their intention to adopt SDM. Descriptive statistical analyses and qualitative thematic analyses were integrated at each round to prioritize training improvements with regard to the determinants most likely to influence participants' intention. Results: Of 106 participants, 98 completed their evaluations of either the e-learning activity or evidence summary (93%). The professions most represented were physicians (60%) and nurses (15%). Professionals valued the e-learning component to gain knowledge on the theory and practice of SDM, and the evidence summaries to apply the knowledge gained through the e-learning activity to diverse clinical contexts. The iterative design process allowed addressing most weaknesses reported. Participants' intentions to adopt SDM and to use the summaries were high at baseline and remained positive as the rounds progressed. Attitude and social influence significantly influenced participants' intention to use the evidence summaries (P < 0.0001). Despite strong intention and the tailoring of tools to users, certain factors external to the training program can still influence the effective use of these tools and the adoption of SDM in practice. Conclusions: A theory-based and user-centered design approach for continuing professional development interventions on SDM with older adults living with neurocognitive disorders and their caregivers appeared useful to identify the most important determinants of learners' intentions to use SDM in their practice, and validate our initial interpretations of learners' assessments during the subsequent evaluation round.
MeSH term(s)	Aged ; Decision Making ; Decision Making, Shared ; Health Personnel ; Humans ; Intention ; Neurocognitive Disorders ; Patient Participation ; Physicians
Language	English
Publishing date	2021-02-17
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2046490-3
ISSN	1472-6947 ; 1472-6947
ISSN (online)	1472-6947
ISSN	1472-6947
DOI	10.1186/s12911-021-01396-y
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Article ; Online: Immune modulation effects of concomitant temozolomide and radiation therapy on peripheral blood mononuclear cells in patients with glioblastoma multiforme.

Fadul, Camilo E / Fisher, Jan L / Gui, Jiang / Hampton, Thomas H / Côté, Anik L / Ernstoff, Marc S

Neuro-oncology

2011 Volume 13, Issue 4, Page(s) 393–400

Abstract: Concomitant radiation therapy (RT) and temozolomide (TMZ) therapy after surgery is the standard treatment for glioblastoma multiforme (GBM). Radiation and chemotherapy can affect the immune system with implications on subsequent immune therapy. Therefore, ...

Abstract	Concomitant radiation therapy (RT) and temozolomide (TMZ) therapy after surgery is the standard treatment for glioblastoma multiforme (GBM). Radiation and chemotherapy can affect the immune system with implications on subsequent immune therapy. Therefore, we examined the phenotype and function of peripheral blood mononuclear cells in 25 patients with GBM prior to and 4 weeks after treatment with RT-TMZ using multicolor flow cytometry, as well as in vitro CD4(+) regulatory T cell (T(reg)) suppressor and dendritic cell maturation assays. RT-TMZ induced significant lymphopenia, with a decrease in total CD4(+) T cells, but did not significantly change monocyte counts. The proportion of functional T(reg) cells increased after treatment, whereas their absolute numbers remained stable. There was also a measurable decrease in the proportion of CD8(+)CD56(+) and absolute number of CD3(-)CD56(+) effector cells. Posttherapy monocytes retained the ability to mature into dendritic cells. Treatment with RT-TMZ is associated with changes in regulatory and effector peripheral blood mononuclear cells that tilt the balance towards an immune suppressive state. This shift can affect the outcome of immune therapy following RT-TMZ treatment and should be considered in the design of future combination therapy regimens.
MeSH term(s)	Adult ; Aged ; Antineoplastic Agents, Alkylating/therapeutic use ; Blood Cells/drug effects ; Blood Cells/immunology ; Blood Cells/radiation effects ; Brain Neoplasms/drug therapy ; Brain Neoplasms/immunology ; Brain Neoplasms/radiotherapy ; Combined Modality Therapy ; Dacarbazine/analogs & derivatives ; Dacarbazine/therapeutic use ; Dendritic Cells/drug effects ; Dendritic Cells/immunology ; Dendritic Cells/radiation effects ; Female ; Flow Cytometry ; Glioblastoma/drug therapy ; Glioblastoma/immunology ; Glioblastoma/radiotherapy ; Humans ; Lymphocyte Subsets ; Male ; Middle Aged ; Prognosis ; Radiotherapy Dosage ; T-Lymphocytes, Regulatory/drug effects ; T-Lymphocytes, Regulatory/immunology ; T-Lymphocytes, Regulatory/radiation effects ; Temozolomide ; Young Adult
Chemical Substances	Antineoplastic Agents, Alkylating ; Dacarbazine (7GR28W0FJI) ; Temozolomide (YF1K15M17Y)
Language	English
Publishing date	2011-02-20
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2028601-6
ISSN	1523-5866 ; 1522-8517
ISSN (online)	1523-5866
ISSN	1522-8517
DOI	10.1093/neuonc/noq204
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Zs.A 5307: Show issues

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Article ; Online: Professional training on shared decision making with older adults living with neurocognitive disorders: a mixed-methods implementation study.

Lawani, Moulikatou Adouni / Côté, Luc / Coudert, Laetitia / Morin, Michèle / Witteman, Holly O / Caron, Danielle / Kroger, Edeltraut / Voyer, Philippe / Rodriguez, Charo / Légaré, France / Giguere, Anik M C

BMC medical informatics and decision making

2020 Volume 20, Issue 1, Page(s) 189

Abstract: Background: Shared decision making with older adults living with neurocognitive disorders is challenging for primary healthcare professionals. We studied the implementation of a professional training program featuring an e-learning activity on shared ... ...

Abstract	Background: Shared decision making with older adults living with neurocognitive disorders is challenging for primary healthcare professionals. We studied the implementation of a professional training program featuring an e-learning activity on shared decision making and five Decision Boxes on the care of people with neurocognitive disorders, and measured the program's effects. Methods: In this mixed-methods study, we recruited healthcare professionals in family medicine clinics and homecare settings in the Quebec City area (Canada). The professionals signed up for training as a continuing professional development activity and answered an online survey before and after training to assess their knowledge, and intention to adopt shared decision making. We recorded healthcare professionals' access to each training component, and conducted telephone interviews with a purposeful sample of extreme cases: half had completed training and the other half had not. We performed bivariate analyses with the survey data and a thematic qualitative analysis of the interviews, as per the theory of planned behaviour. Results: Of the 47 participating healthcare professionals, 31 (66%) completed at least one training component. Several factors restricted participation, including lack of time, training fragmentation into several components, poor adaptation of training to specific professions, and technical/logistical barriers. Ease of access, ease of use, the usefulness of training content and the availability of training credits fostered participation. Training allowed Healthcare professionals to improve their knowledge about risk communication (p = 0.02), and their awareness of the options (P = 0.011). Professionals' intention to adopt shared decision making was high before training (mean ± SD = 5.88 ± 0.99, scale from 1 to 7, with 7 high) and remained high thereafter (5.94 ± 0.9). Conclusions: The results of this study will allow modifying the training program to improve participation rates and, ultimately, uptake of meaningful shared decision making with patients living with neurocognitive disorders.
MeSH term(s)	Aged ; Aged, 80 and over ; Aging ; Canada ; Decision Making ; Decision Making, Shared ; Dementia/diagnosis ; Dementia/therapy ; Female ; Health Personnel ; Humans ; Implementation Science ; Male ; Neurocognitive Disorders/diagnosis ; Neurocognitive Disorders/psychology ; Patient Participation ; Primary Health Care ; Quebec
Language	English
Publishing date	2020-08-12
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2046490-3
ISSN	1472-6947 ; 1472-6947
ISSN (online)	1472-6947
ISSN	1472-6947
DOI	10.1186/s12911-020-01197-9
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Article: Induction of postsurgical tumor immunity and T-cell memory by a poorly immunogenic tumor.

Zhang, Peisheng / Côté, Anik L / de Vries, Victor C / Usherwood, Edward J / Turk, Mary Jo

Cancer research

2007 Volume 67, Issue 13, Page(s) 6468–6476

Abstract: The generation of protective CD8 T-cell memory against tumor-expressed self-antigens is an important but elusive goal of cancer immunotherapy. The possibility that a progressive, poorly immunogenic tumor can induce T-cell memory against self-antigens has ...

Abstract	The generation of protective CD8 T-cell memory against tumor-expressed self-antigens is an important but elusive goal of cancer immunotherapy. The possibility that a progressive, poorly immunogenic tumor can induce T-cell memory against self-antigens has not previously been studied. Herein, we report that growth of the poorly immunogenic B16 melanoma in the absence of regulatory T cells (T(reg)) generates CD8 T-cell responses that develop into functional memory after the tumor has been surgically excised. Tumor-primed memory T cells recognized melanocyte differentiation antigens TRP-2/DCT and gp100 and persisted for as long as 5 months following surgical tumor excision. Phenotypic analysis showed that these cells develop into both central and effector memory T-cell subsets, which produce IFN-gamma and interleukin-2 on reencounter with antigen. Most importantly, tumor-primed memory T cells mediated the rejection of intradermal and systemically disseminated challenge tumors given 30 to 60 days following surgery. Tumor-excised mice also developed autoimmune vitiligo, showing that T(reg) cells prevent tissue-specific autoimmunity in tumor-bearing hosts. This study establishes that T(reg) depletion in tumor-bearing hosts drives the natural development of protective T-cell memory. Generating such responses may aid in the clinical management of tumor recurrence and metastasis following surgery.
MeSH term(s)	Animals ; Autoimmune Diseases/immunology ; CD4-Positive T-Lymphocytes/metabolism ; Cytokines/metabolism ; Immunologic Memory ; Immunotherapy/methods ; Interferon-gamma/metabolism ; Interleukin-2/metabolism ; Male ; Melanoma, Experimental/immunology ; Melanoma, Experimental/pathology ; Mice ; Mice, Inbred C57BL ; Postoperative Period ; T-Lymphocytes/immunology ; T-Lymphocytes/metabolism ; Vitiligo/immunology
Chemical Substances	Cytokines ; Interleukin-2 ; Interferon-gamma (82115-62-6)
Language	English
Publishing date	2007-07-01
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1432-1
ISSN	1538-7445 ; 0008-5472
ISSN (online)	1538-7445
ISSN	0008-5472
DOI	10.1158/0008-5472.CAN-07-1264
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Article ; Online: Gene expression profile of peripheral blood lymphocytes from renal cell carcinoma patients treated with IL-2, interferon-α and dendritic cell vaccine.

Wolf, Benita / Schwarzer, Adrian / Côté, Anik L / Hampton, Thomas H / Schwaab, Thomas / Huarte, Eduardo / Tomlinson, Craig R / Gui, Jiang / Fisher, Jan L / Fadul, Camilo E / Hamilton, Joshua W / Ernstoff, Marc S

PloS one

2012 Volume 7, Issue 12, Page(s) e50221

Abstract: Lymphocytes are a key component of the immune system and their differentiation and function are directly influenced by cancer. We examined peripheral blood lymphocyte (PBL) gene expression as a biomarker of illness and treatment effect using the ... ...

Abstract	Lymphocytes are a key component of the immune system and their differentiation and function are directly influenced by cancer. We examined peripheral blood lymphocyte (PBL) gene expression as a biomarker of illness and treatment effect using the Affymetrix Human Gene ST1 platform in patients with metastatic renal cell carcinoma (mRCC) who received combined treatment with IL-2, interferon-?-2a and dendritic cell vaccine. We examined gene expression, cytokine levels in patient serum and lymphocyte subsets as determined by flow cytometry (FCM). Pre-treatment PBLs from patients with mRCC exhibit a gene expression profile and serum cytokine profile consistent with inflammation and proliferation not found in healthy donors (HD). PBL gene expression from patients with mRCC showed increased mRNA of genes involved with T-cell and T(REG)-cell activation pathways, which was also reflected in lymphocyte subset distribution. Overall, PBL gene expression post-treatment (POST) was not significantly different than pre-treatment (PRE). Nevertheless, treatment related changes in gene expression (post-treatment minus pre-treatment) revealed an increased expression of T-cell and B-cell receptor signaling pathways in responding (R) patients compared to non-responding (NR) patients. In addition, we observed down-regulation of T(REG)-cell pathways post-treatment in R vs. NR patients. While exploratory in nature, this study supports the hypothesis that enhanced inflammatory cytotoxic pathways coupled with blunting of the regulatory pathways is necessary for effective anti-cancer activity associated with immune therapy. This type of analysis can potentially identify additional immune therapeutic targets in patients with mRCC.
MeSH term(s)	Cancer Vaccines/therapeutic use ; Carcinoma, Renal Cell/blood ; Carcinoma, Renal Cell/genetics ; Carcinoma, Renal Cell/therapy ; Cluster Analysis ; Cytokines/blood ; Dendritic Cells/immunology ; Female ; Flow Cytometry ; Gene Expression Profiling ; Humans ; Interferon-alpha/therapeutic use ; Interleukin-2/therapeutic use ; Kidney Neoplasms/blood ; Kidney Neoplasms/genetics ; Kidney Neoplasms/therapy ; Lymphocyte Subsets ; Lymphocytes/metabolism ; Male ; Middle Aged ; Oligonucleotide Array Sequence Analysis ; Real-Time Polymerase Chain Reaction
Chemical Substances	Cancer Vaccines ; Cytokines ; Interferon-alpha ; Interleukin-2
Language	English
Publishing date	2012-12-03
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0050221
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In stock of ZB MED Cologne/Königswinter

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More links

Kategorien

Order via subito

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