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Article ; Online: Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance.

Bagchi, Sreya / Yuan, Robert / Engleman, Edgar G

2020 Volume 16, Page(s) 223–249

Abstract: Immune checkpoint inhibitors (ICIs) have made an indelible mark in the field of cancer immunotherapy. Starting with the approval of anti-cytotoxic T lymphocyte-associated protein 4 (anti-CTLA-4) for advanced-stage melanoma in 2011, ICIs-which now also ... ...

Abstract	Immune checkpoint inhibitors (ICIs) have made an indelible mark in the field of cancer immunotherapy. Starting with the approval of anti-cytotoxic T lymphocyte-associated protein 4 (anti-CTLA-4) for advanced-stage melanoma in 2011, ICIs-which now also include antibodies against programmed cell death 1 (PD-1) and its ligand (PD-L1)-quickly gained US Food and Drug Administration approval for the treatment of a wide array of cancer types, demonstrating unprecedented extension of patient survival. However, despite the success of ICIs, resistance to these agents restricts the number of patients able to achieve durable responses, and immune-related adverse events complicate treatment. Thus, a better understanding of the requirements for an effective and safe antitumor immune response following ICI therapy is needed. Studies of both tumoral and systemic changes in the immune system following ICI therapy have yielded insight into the basis for both efficacy and resistance. Ultimately, by building on these insights, researchers should be able to combine ICIs with other agents, or design new immunotherapies, to achieve broader and more durable efficacy as well as greater safety. Here, we review the history and clinical utility of ICIs, the mechanisms of resistance to therapy, and local and systemic immune cell changes associated with outcome.
MeSH term(s)	Animals ; Drug Resistance, Neoplasm/physiology ; Humans ; Immune Checkpoint Inhibitors/therapeutic use ; Immunotherapy/methods ; Neoplasms/drug therapy ; Neoplasms/immunology
Chemical Substances	Immune Checkpoint Inhibitors
Keywords	covid19
Language	English
Publishing date	2020-11-16
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	2227429-7
ISSN	1553-4014 ; 1553-4006
ISSN (online)	1553-4014
ISSN	1553-4006
DOI	10.1146/annurev-pathol-042020-042741
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Article: Linking CD1-Restricted T Cells With Autoimmunity and Dyslipidemia: Lipid Levels Matter.

Bagchi, Sreya / Genardi, Samantha / Wang, Chyung-Ru

Frontiers in immunology

2018 Volume 9, Page(s) 1616

Abstract: Dyslipidemia, or altered blood lipid content, is a risk factor for developing cardiovascular disease. Furthermore, several autoimmune diseases, including systemic lupus erythematosus, psoriasis, diabetes, and rheumatoid arthritis, are correlated highly ... ...

Abstract	Dyslipidemia, or altered blood lipid content, is a risk factor for developing cardiovascular disease. Furthermore, several autoimmune diseases, including systemic lupus erythematosus, psoriasis, diabetes, and rheumatoid arthritis, are correlated highly with dyslipidemia. One common thread between both autoimmune diseases and altered lipid levels is the presence of inflammation, suggesting that the immune system might act as the link between these related pathologies. Deciphering the role of innate and adaptive immune responses in autoimmune diseases and, more recently, obesity-related inflammation, have been active areas of research. The broad picture suggests that antigen-presenting molecules, which present self-peptides to autoreactive T cells, can result in either aggravation or amelioration of inflammation. However, very little is known about the role of self-lipid reactive T cells in dyslipidemia-associated autoimmune events. Given that a range of autoimmune diseases are linked to aberrant lipid profiles and a majority of lipid-specific T cells are reactive to self-antigens, it is important to examine the role of these T cells in dyslipidemia-related autoimmune ailments and determine if dysregulation of these T cells can be drivers of autoimmune conditions. CD1 molecules present lipids to T cells and are divided into two groups based on sequence homology. To date, most of the information available on lipid-reactive T cells comes from the study of group 2 CD1d-restricted natural killer T (NKT) cells while T cells reactive to group 1 CD1 molecules remain understudied, despite their higher abundance in humans compared to NKT cells. This review evaluates the mechanisms by which CD1-reactive, self-lipid specific T cells contribute to dyslipidemia-associated autoimmune disease progression or amelioration by examining available literature on NKT cells and highlighting recent progress made on the study of group 1 CD1-restricted T cells.
Language	English
Publishing date	2018-07-16
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2606827-8
ISSN	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2018.01616
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Article: Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance

Bagchi, Sreya / Yuan, Robert / Engleman, Edgar G

Annual review of pathology (Online)

Abstract	Immune checkpoint inhibitors (ICIs) have made an indelible mark in the field of cancer immunotherapy. Starting with the approval of anti-cytotoxic T lymphocyte-associated protein 4 (anti-CTLA-4) for advanced-stage melanoma in 2011, ICIs-which now also include antibodies against programmed cell death 1 (PD-1) and its ligand (PD-L1)-quickly gained US Food and Drug Administration approval for the treatment of a wide array of cancer types, demonstrating unprecedented extension of patient survival. However, despite the success of ICIs, resistance to these agents restricts the number of patients able to achieve durable responses, and immune-related adverse events complicate treatment. Thus, a better understanding of the requirements for an effective and safe antitumor immune response following ICI therapy is needed. Studies of both tumoral and systemic changes in the immune system following ICI therapy have yielded insight into the basis for both efficacy and resistance. Ultimately, by building on these insights, researchers should be able to combine ICIs with other agents, or design new immunotherapies, to achieve broader and more durable efficacy as well as greater safety. Here, we review the history and clinical utility of ICIs, the mechanisms of resistance to therapy, and local and systemic immune cell changes associated with outcome. Expected final online publication date for the Annual Review of Pathology: Mechanisms of Disease, Volume 16 is January 25, 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
Keywords	covid19
Publisher	WHO
Document type	Article
Note	WHO #Covidence: #33197221
Database	COVID19

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Article: CD1b-autoreactive T cells recognize phospholipid antigens and contribute to antitumor immunity against a CD1b

Bagchi, Sreya / Li, Sha / Wang, Chyung-Ru

Oncoimmunology

2016 Volume 5, Issue 9, Page(s) e1213932

Abstract: Adoptive immunotherapy for cancer treatment is an emerging field of study. Till now, several tumor-derived, peptide-specific T cell responses have been harnessed for treating cancers. However, the contribution of lipid-specific T cells in tumor immunity ... ...

Abstract	Adoptive immunotherapy for cancer treatment is an emerging field of study. Till now, several tumor-derived, peptide-specific T cell responses have been harnessed for treating cancers. However, the contribution of lipid-specific T cells in tumor immunity has been understudied. CD1 molecules, which present self- and foreign lipid antigens to T cells, are divided into group 1 (CD1a, CD1b, and CD1c) and group 2 (CD1d). Although the role of CD1d-restricted natural killer T cells (NKT) in several tumor models has been well established, the contribution of group 1 CD1-restricted T cells in tumor immunity remains obscure due to the lack of group 1 CD1 expression in mice. In this study, we used a double transgenic mouse model expressing human group 1 CD1 molecules (hCD1Tg) and a CD1b-restricted, self-lipid reactive T cell receptor (HJ1Tg) to study the potential role of group 1 CD1-restricted autoreactive T cells in antitumor response. We found that HJ1 T cells recognized phospholipids and responded more potently to lipid extracted from tumor cells than the equivalent amount of lipids extracted from normal cells. Additionally, the autoreactivity of HJ1 T cells was enhanced upon treatment with various intracellular toll-like receptor (TLR) agonists, including CpG oligodeoxynucleotides (ODN), R848, and poly (I:C). Interestingly, the adoptive transfer of HJ1 T cells conferred protection against the CD1b-transfected murine T cell lymphoma (RMA-S/CD1b) and CpG ODN enhanced the antitumor effect. Thus, this study, for the first time, demonstrates the antitumor potential of CD1b-autoreactive T cells and their potential use in adoptive immunotherapy.
Language	English
Publishing date	2016-07-22
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2645309-5
ISSN	2162-402X ; 2162-4011
ISSN (online)	2162-402X
ISSN	2162-4011
DOI	10.1080/2162402X.2016.1213932
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Type II natural killer T cells foster the antitumor activity of CpG-oligodeoxynucleotides.

Zhao, Jie / Bagchi, Sreya / Wang, Chyung-Ru

Oncoimmunology

2014 Volume 3, Page(s) e28977

Abstract: Type II natural killer T (NKT) cells in cancer immunity are typically associated with suppression of tumor immunosurveillance through secretion of IL-13. We previously demonstrated that CpG oligonucleotide therapy activated Type II NKT cells to produce T ...

Abstract	Type II natural killer T (NKT) cells in cancer immunity are typically associated with suppression of tumor immunosurveillance through secretion of IL-13. We previously demonstrated that CpG oligonucleotide therapy activated Type II NKT cells to produce T helper type 1 (Th1) rather than T helper type 2 (Th2) cytokines. This cytokine skewing may manifest in Type II NKT cell antitumor properties in an immunotherapeutic setting.
Language	English
Publishing date	2014-05-23
Publishing country	United States
Document type	Journal Article
ZDB-ID	2645309-5
ISSN	2162-402X ; 2162-4011
ISSN (online)	2162-402X
ISSN	2162-4011
DOI	10.4161/onci.28977
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Article: Enteric Glia Play a Critical Role in Promoting the Development of Colorectal Cancer.

Yuan, Robert / Bhattacharya, Nupur / Kenkel, Justin A / Shen, Jeanne / DiMaio, Michael A / Bagchi, Sreya / Prestwood, Tyler R / Habtezion, Aida / Engleman, Edgar G

Frontiers in oncology

2020 Volume 10, Page(s) 595892

Abstract: Enteric glia are a distinct population of peripheral glial cells in the enteric nervous system that regulate intestinal homeostasis, epithelial barrier integrity, and gut defense. Given these unique attributes, we investigated the impact of enteric glia ... ...

Abstract	Enteric glia are a distinct population of peripheral glial cells in the enteric nervous system that regulate intestinal homeostasis, epithelial barrier integrity, and gut defense. Given these unique attributes, we investigated the impact of enteric glia depletion on tumor development in azoxymethane/dextran sodium sulfate (AOM/DSS)-treated mice, a classical model of colorectal cancer (CRC). Depleting GFAP
Language	English
Publishing date	2020-11-13
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2649216-7
ISSN	2234-943X
ISSN	2234-943X
DOI	10.3389/fonc.2020.595892
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Article ; Online: Polyclonal type II natural killer T cells require PLZF and SAP for their development and contribute to CpG-mediated antitumor response.

Zhao, Jie / Weng, Xiufang / Bagchi, Sreya / Wang, Chyung-Ru

Proceedings of the National Academy of Sciences of the United States of America

2014 Volume 111, Issue 7, Page(s) 2674–2679

Abstract: CD1d-restricted natural killer T (NKT) cells are innate-like T cells with potent immunomodulatory function via rapid production of both Th1 and Th2 cytokines. NKT cells comprise well-characterized type I NKT cells, which can be detected by α- ... ...

Abstract	CD1d-restricted natural killer T (NKT) cells are innate-like T cells with potent immunomodulatory function via rapid production of both Th1 and Th2 cytokines. NKT cells comprise well-characterized type I NKT cells, which can be detected by α-galactosylceramide-loaded CD1d tetramers, and less-studied type II NKT cells, which do not recognize α-galactosylceramide. Here we characterized type II NKT cells on a polyclonal level by using a Jα18-deficient IL-4 reporter mouse model. This model allows us to track type II NTK cells by the GFP(+)TCRβ(+) phenotype in the thymus and liver. We found type II NKT cells, like type I NKT cells, exhibit an activated phenotype and are dependent on the transcriptional regulator promyelocytic leukemia zinc finger (PLZF) and the adaptor molecule signaling lymphocyte activation molecule-associated protein (SAP) for their development. Type II NKT cells are potently activated by β-D-glucopyranosylceramide (β-GlcCer) but not sulfatide or phospholipids in a CD1d-dependent manner, with the stimulatory capacity of β-GlcCer influenced by acyl chain length. Compared with type I NKT cells, type II NKT cells produce lower levels of IFN-γ but comparable amounts of IL-13 in response to polyclonal T-cell receptor stimulation, suggesting they may play different roles in regulating immune responses. Furthermore, type II NKT cells can be activated by CpG oligodeoxynucletides to produce IFN-γ, but not IL-4 or IL-13. Importantly, CpG-activated type II NKT cells contribute to the antitumor effect of CpG in the B16 melanoma model. Taken together, our data reveal the characteristics of polyclonal type II NKT cells and their potential role in antitumor immunotherapy.
MeSH term(s)	Animals ; CpG Islands/genetics ; DNA Primers/genetics ; Flow Cytometry ; Green Fluorescent Proteins/metabolism ; Immunomodulation/immunology ; Intracellular Signaling Peptides and Proteins/immunology ; Intracellular Signaling Peptides and Proteins/metabolism ; Kruppel-Like Transcription Factors/immunology ; Kruppel-Like Transcription Factors/metabolism ; Melanoma, Experimental/immunology ; Melanoma, Experimental/therapy ; Mice ; Mice, Knockout ; Natural Killer T-Cells/immunology ; Promyelocytic Leukemia Zinc Finger Protein ; Real-Time Polymerase Chain Reaction ; Reverse Transcriptase Polymerase Chain Reaction ; Signaling Lymphocytic Activation Molecule Associated Protein
Chemical Substances	DNA Primers ; Intracellular Signaling Peptides and Proteins ; Kruppel-Like Transcription Factors ; Promyelocytic Leukemia Zinc Finger Protein ; Sh2d1a protein, mouse ; Signaling Lymphocytic Activation Molecule Associated Protein ; Zbtb16 protein, mouse ; Green Fluorescent Proteins (147336-22-9)
Language	English
Publishing date	2014-02-03
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	209104-5
ISSN	1091-6490 ; 0027-8424
ISSN (online)	1091-6490
ISSN	0027-8424
DOI	10.1073/pnas.1323845111
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Article ; Online: Lymph node colonization induces tumor-immune tolerance to promote distant metastasis.

Reticker-Flynn, Nathan E / Zhang, Weiruo / Belk, Julia A / Basto, Pamela A / Escalante, Nichole K / Pilarowski, Genay O W / Bejnood, Alborz / Martins, Maria M / Kenkel, Justin A / Linde, Ian L / Bagchi, Sreya / Yuan, Robert / Chang, Serena / Spitzer, Matthew H / Carmi, Yaron / Cheng, Jiahan / Tolentino, Lorna L / Choi, Okmi / Wu, Nancy /

Kong, Christina S / Gentles, Andrew J / Sunwoo, John B / Satpathy, Ansuman T / Plevritis, Sylvia K / Engleman, Edgar G

Cell

2022 Volume 185, Issue 11, Page(s) 1924–1942.e23

Abstract: For many solid malignancies, lymph node (LN) involvement represents a harbinger of distant metastatic disease and, therefore, an important prognostic factor. Beyond its utility as a biomarker, whether and how LN metastasis plays an active role in shaping ...

Abstract	For many solid malignancies, lymph node (LN) involvement represents a harbinger of distant metastatic disease and, therefore, an important prognostic factor. Beyond its utility as a biomarker, whether and how LN metastasis plays an active role in shaping distant metastasis remains an open question. Here, we develop a syngeneic melanoma mouse model of LN metastasis to investigate how tumors spread to LNs and whether LN colonization influences metastasis to distant tissues. We show that an epigenetically instilled tumor-intrinsic interferon response program confers enhanced LN metastatic potential by enabling the evasion of NK cells and promoting LN colonization. LN metastases resist T cell-mediated cytotoxicity, induce antigen-specific regulatory T cells, and generate tumor-specific immune tolerance that subsequently facilitates distant tumor colonization. These effects extend to human cancers and other murine cancer models, implicating a conserved systemic mechanism by which malignancies spread to distant organs.
MeSH term(s)	Animals ; Immune Tolerance ; Immunotherapy ; Lymph Nodes ; Lymphatic Metastasis/pathology ; Melanoma/pathology ; Mice
Language	English
Publishing date	2022-05-06
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	187009-9
ISSN	1097-4172 ; 0092-8674
ISSN (online)	1097-4172
ISSN	0092-8674
DOI	10.1016/j.cell.2022.04.019
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Zs.A 1167: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: CD1b-autoreactive T cells contribute to hyperlipidemia-induced skin inflammation in mice.

Bagchi, Sreya / He, Ying / Zhang, Hong / Cao, Liang / Van Rhijn, Ildiko / Moody, D Branch / Gudjonsson, Johann E / Wang, Chyung-Ru

The Journal of clinical investigation

2017 Volume 127, Issue 6, Page(s) 2339–2352

Abstract: A large proportion of human T cells are autoreactive to group 1 CD1 proteins, which include CD1a, CD1b, and CD1c. However, the physiological role of the CD1 proteins remains poorly defined. Here, we have generated a double-transgenic mouse model that ... ...

Abstract	A large proportion of human T cells are autoreactive to group 1 CD1 proteins, which include CD1a, CD1b, and CD1c. However, the physiological role of the CD1 proteins remains poorly defined. Here, we have generated a double-transgenic mouse model that expresses human CD1b and CD1c molecules (hCD1Tg) as well as a CD1b-autoreactive TCR (HJ1Tg) in the ApoE-deficient background (hCD1Tg HJ1Tg Apoe-/- mice) to determine the role of CD1-autoreactive T cells in hyperlipidemia-associated inflammatory diseases. We found that hCD1Tg HJ1Tg Apoe-/- mice spontaneously developed psoriasiform skin inflammation characterized by T cell and neutrophil infiltration and a Th17-biased cytokine response. Anti-IL-17A treatment ameliorated skin inflammation in vivo. Additionally, phospholipids and cholesterol preferentially accumulated in diseased skin and these autoantigens directly activated CD1b-autoreactive HJ1 T cells. Furthermore, hyperlipidemic serum enhanced IL-6 secretion by CD1b+ DCs and increased IL-17A production by HJ1 T cells. In psoriatic patients, the frequency of CD1b-autoreactive T cells was increased compared with that in healthy controls. Thus, this study has demonstrated the pathogenic role of CD1b-autoreactive T cells under hyperlipidemic conditions in a mouse model of spontaneous skin inflammation. As a large proportion of psoriatic patients are dyslipidemic, this finding is of clinical significance and indicates that self-lipid-reactive T cells might serve as a possible link between hyperlipidemia and psoriasis.
MeSH term(s)	Animals ; Antigens, CD1/metabolism ; Cells, Cultured ; Coculture Techniques ; Dermatitis/immunology ; Humans ; Hyperlipidemias/complications ; Hyperlipidemias/immunology ; Lymphocyte Activation ; Mice, Knockout ; Neutrophil Infiltration ; Psoriasis/immunology ; Skin/immunology ; Skin/pathology ; T-Lymphocytes/immunology
Chemical Substances	Antigens, CD1 ; CD1b antigen
Language	English
Publishing date	2017-06-01
Publishing country	United States
Document type	Journal Article
ZDB-ID	3067-3
ISSN	1558-8238 ; 0021-9738
ISSN (online)	1558-8238
ISSN	0021-9738
DOI	10.1172/JCI92217
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Article: Lymph node colonization induces tumor-immune tolerance to promote distant metastasis

Reticker-Flynn, Nathan E. / Zhang, Weiruo / Belk, Julia A. / Basto, Pamela A. / Escalante, Nichole K. / Pilarowski, Genay O.W. / Bejnood, Alborz / Martins, Maria M. / Kenkel, Justin A. / Linde, Ian L. / Bagchi, Sreya / Yuan, Robert / Chang, Serena / Spitzer, Matthew H. / Carmi, Yaron / Cheng, Jiahan / Tolentino, Lorna L. / Choi, Okmi / Wu, Nancy /

Kong, Christina S. / Gentles, Andrew J. / Sunwoo, John B. / Satpathy, Ansuman T. / Plevritis, Sylvia K. / Engleman, Edgar G.

Cell. 2022 May 26, v. 185, no. 11

2022

Abstract	For many solid malignancies, lymph node (LN) involvement represents a harbinger of distant metastatic disease and, therefore, an important prognostic factor. Beyond its utility as a biomarker, whether and how LN metastasis plays an active role in shaping distant metastasis remains an open question. Here, we develop a syngeneic melanoma mouse model of LN metastasis to investigate how tumors spread to LNs and whether LN colonization influences metastasis to distant tissues. We show that an epigenetically instilled tumor-intrinsic interferon response program confers enhanced LN metastatic potential by enabling the evasion of NK cells and promoting LN colonization. LN metastases resist T cell-mediated cytotoxicity, induce antigen-specific regulatory T cells, and generate tumor-specific immune tolerance that subsequently facilitates distant tumor colonization. These effects extend to human cancers and other murine cancer models, implicating a conserved systemic mechanism by which malignancies spread to distant organs.
Keywords	biomarkers ; cytotoxicity ; humans ; immunosuppression ; interferons ; lymph nodes ; melanoma ; metastasis ; mice
Language	English
Dates of publication	2022-0526
Size	p. 1924-1942.e23.
Publishing place	Elsevier Inc.
Document type	Article
ZDB-ID	187009-9
ISSN	1097-4172 ; 0092-8674
ISSN (online)	1097-4172
ISSN	0092-8674
DOI	10.1016/j.cell.2022.04.019
Database	NAL-Catalogue (AGRICOLA)

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