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Article: Harnessing Antitumor CD4

Ben Khelil, Myriam / Godet, Yann / Abdeljaoued, Syrine / Borg, Christophe / Adotévi, Olivier / Loyon, Romain

2022 Volume 14, Issue 1

Abstract: Over the past decades, ... ...

Abstract	Over the past decades, CD4
Language	English
Publishing date	2022-01-05
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers14010260
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Article ; Online: Tissue-resident memory T cells in gastrointestinal cancer immunology and immunotherapy: ready for prime time?

Abdeljaoued, Syrine / Arfa, Sara / Kroemer, Marie / Ben Khelil, Myriam / Vienot, Angélique / Heyd, Bruno / Loyon, Romain / Doussot, Alexandre / Borg, Christophe

Journal for immunotherapy of cancer

2022 Volume 10, Issue 4

Abstract: Tissue-resident memory T ( ... ...

Abstract	Tissue-resident memory T (T
MeSH term(s)	Epigenesis, Genetic ; Gastrointestinal Neoplasms/therapy ; Humans ; Immunotherapy ; Memory T Cells ; Tumor Microenvironment
Language	English
Publishing date	2022-04-25
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2719863-7
ISSN	2051-1426 ; 2051-1426
ISSN (online)	2051-1426
ISSN	2051-1426
DOI	10.1136/jitc-2021-003472
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Article ; Online: Chemokine switch regulated by TGF-β1 in cancer-associated fibroblast subsets determines the efficacy of chemo-immunotherapy.

Vienot, Angélique / Pallandre, Jean-René / Renaude, Elodie / Viot, Julien / Bouard, Adeline / Spehner, Laurie / Kroemer, Marie / Abdeljaoued, Syrine / van der Woning, Bas / de Haard, Hans / Loyon, Romain / Hervouet, Eric / Peixoto, Paul / Borg, Christophe

Oncoimmunology

2022 Volume 11, Issue 1, Page(s) 2144669

Abstract: Combining immunogenic cell death-inducing chemotherapies and PD-1 blockade can generate remarkable tumor responses. It is now well established that TGF-β1 signaling is a major component of treatment resistance and contributes to the cancer-related ... ...

Abstract	Combining immunogenic cell death-inducing chemotherapies and PD-1 blockade can generate remarkable tumor responses. It is now well established that TGF-β1 signaling is a major component of treatment resistance and contributes to the cancer-related immunosuppressive microenvironment. However, whether TGF-β1 remains an obstacle to immune checkpoint inhibitor efficacy when immunotherapy is combined with chemotherapy is still to be determined. Several syngeneic murine models were used to investigate the role of TGF-β1 neutralization on the combinations of immunogenic chemotherapy (FOLFOX: 5-fluorouracil and oxaliplatin) and anti-PD-1. Cancer-associated fibroblasts (CAF) and immune cells were isolated from CT26 and PancOH7 tumor-bearing mice treated with FOLFOX, anti-PD-1 ± anti-TGF-β1 for bulk and single cell RNA sequencing and characterization. We showed that TGF-β1 neutralization promotes the therapeutic efficacy of FOLFOX and anti-PD-1 combination and induces the recruitment of antigen-specific CD8
MeSH term(s)	Mice ; Animals ; Cancer-Associated Fibroblasts/pathology ; CD8-Positive T-Lymphocytes ; Immunotherapy/methods ; Chemokines/therapeutic use ; Neoplasms/drug therapy ; Tumor Microenvironment
Chemical Substances	Chemokines
Language	English
Publishing date	2022-11-12
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2645309-5
ISSN	2162-402X ; 2162-4011
ISSN (online)	2162-402X
ISSN	2162-4011
DOI	10.1080/2162402X.2022.2144669
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Article ; Online: Anti-Telomerase CD4

Spehner, Laurie / Kim, Stefano / Vienot, Angélique / François, Eric / Buecher, Bruno / Adotevi, Olivier / Vernerey, Dewi / Abdeljaoued, Syrine / Meurisse, Aurélia / Borg, Christophe

International journal of molecular sciences

2020 Volume 21, Issue 18

Abstract: Docetaxel, cisplatin and 5-fluorouracil (DCF) chemotherapy regimen is highly effective in advanced anal squamous cell carcinoma (SCCA), as demonstrated by the Epitopes-HPV02 study results. Here, we analyzed the impact of DCF regimen and the prognostic ... ...

Abstract	Docetaxel, cisplatin and 5-fluorouracil (DCF) chemotherapy regimen is highly effective in advanced anal squamous cell carcinoma (SCCA), as demonstrated by the Epitopes-HPV02 study results. Here, we analyzed the impact of DCF regimen and the prognostic value of adaptive immune responses and immunosuppressive cells in SCCA patients included in two prospective studies (Epitopes-HPV01 and HPV02). The presence of T-cell responses against Human papillomavirus (HPV)16-E6/E7 and anti-telomerase (hTERT)-antigens was measured by IFNᵧ-ELISpot. Here, we showed that HPV-adaptive immune responses are increased in SCCA patients. SCCA patients also displayed enhanced circulating TH1 T-cells restricted by hTERT. Exposition to DCF increased hTERT immunity but not HPV or common viruses immune responses. Notably, the correlation of hTERT immune responses with SCCA patients' clinical outcomes highlights that hTERT is a relevant antigen in this HPV-related disease. The influence of peripheral immunosuppressive cells was investigated by flow cytometry. While both regulatory T-cells and monocytic-myeloid-derived suppressive cells (M-MDSC) accumulated in the peripheral blood of SCCA patients, only high levels of M-MDSC were negatively correlated with hTERT adaptive immune responses and predicted poor prognosis. Altogether, our results reveal that hTERT is a relevant antigen in HPV-driven SCCA disease and that M-MDSC levels influence TH1-adaptive immune responses and patients' survival.
MeSH term(s)	Adaptive Immunity ; Adult ; Aged ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Anus Neoplasms/drug therapy ; Anus Neoplasms/immunology ; Anus Neoplasms/pathology ; Anus Neoplasms/virology ; CD4-Positive T-Lymphocytes ; Carcinoma, Squamous Cell/drug therapy ; Carcinoma, Squamous Cell/immunology ; Carcinoma, Squamous Cell/mortality ; Carcinoma, Squamous Cell/virology ; Cisplatin/therapeutic use ; Docetaxel/therapeutic use ; Female ; Fluorouracil/therapeutic use ; Humans ; Male ; Middle Aged ; Papillomavirus Infections/immunology ; Papillomavirus Infections/pathology ; Prognosis ; Prospective Studies ; Telomerase/immunology ; Th1 Cells/immunology
Chemical Substances	Docetaxel (15H5577CQD) ; Telomerase (EC 2.7.7.49) ; Cisplatin (Q20Q21Q62J) ; Fluorouracil (U3P01618RT)
Language	English
Publishing date	2020-09-17
Publishing country	Switzerland
Document type	Clinical Trial, Phase II ; Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms21186838
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Article ; Online: A new workflow combining magnetic cell separation and impedance-based cell dispensing for gentle, simple and reliable cloning of specific CD8+ T cells.

Ben Khelil, Myriam / Aeberli, Luc / Perchaud, Marie / Genolet, Raphael / Abdeljaoued, Syrine / Borg, Christophe / Binda, Delphine / Harari, Alexandre / Jandus, Camilla / Muller, Georges / Loyon, Romain

SLAS technology

2021 Volume 27, Issue 2, Page(s) 130–134

Abstract: Reverse immunology has open the door to innovative cancer immunotherapy strategies such as immunogenic antigen-based vaccination and transgenic T cell receptor (TCR)-based adoptive cell transfer. This approach enables the identification of immunogenic ... ...

Abstract	Reverse immunology has open the door to innovative cancer immunotherapy strategies such as immunogenic antigen-based vaccination and transgenic T cell receptor (TCR)-based adoptive cell transfer. This approach enables the identification of immunogenic tumor specific antigen derived peptides. One of the major challenges is the rapid selection of antigen-specific CD8+ T cell clones. Thus, IFNγ-producing CD8+ T cells magnetic sorting combined with limiting dilution cloning approach represents the most common method of specific T cell cloning. However, during plate setup several wells will not contain T cells whereas others will contain mixed population of T cells. In this case, a re-cloning step is required which make limiting dilution based cloning a laborious, inefficient, expensive and a time-consuming method. To address these obstacles, here we present a novel 2-step workflow combining simple, affordable and gentle magnetic cell separation followed by single cell isolation using a device called DispenCell-S1. We aimed to compare this new workflow with the traditional limiting dilution method using in vitro generated antigen-specific CD8+ T cells. Herein, we reported the reliability of DispenCell-S1 method and its efficiency in T cell clones isolation.
MeSH term(s)	CD8-Positive T-Lymphocytes ; Cell Separation ; Cloning, Molecular ; Electric Impedance ; Reproducibility of Results ; Workflow
Language	English
Publishing date	2021-12-04
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2900310-6
ISSN	2472-6311 ; 2472-6303
ISSN (online)	2472-6311
ISSN	2472-6303
DOI	10.1016/j.slast.2021.11.001
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Article ; Online: MARCKS protein overexpression is associated with poor prognosis in male breast cancer.

Manai, Maroua / Abdeljaoued, Syrine / Goucha, Aïda / Adouni, Olfa / Bettaieb, Ilhem / Bouzaien, Hatem / Rahal, Khaled / Birnbaum, Daniel / Bertucci, François / Gamoudi, Amor

Cancer biomarkers : section A of Disease markers

2019 Volume 26, Issue 4, Page(s) 513–522

Abstract: Background: Male breast cancer (MBC) is a rare and aggressive disease. Thus, identification of new therapeutic targets is crucial.: Objective: Our objective was to evaluate the protein expression of MARCKS (Myristoylated Alanine-Rich C-Kinase ... ...

Abstract	Background: Male breast cancer (MBC) is a rare and aggressive disease. Thus, identification of new therapeutic targets is crucial. Objective: Our objective was to evaluate the protein expression of MARCKS (Myristoylated Alanine-Rich C-Kinase Substrate) in MBC and to investigate its prognostic value. Materials and methods: MARCKS protein expression in tumor and stromal cells was analyzed by immunohistochemistry (IHC) in a retrospective series of 96 pre-chemotherapy MBC samples and 80 normal breast samples, from Tunisian patients treated at Salah Azaiez Institute. Correlations were searched between MARCKS expression and clinicopathological features including overall survival (OS). Results: MARCKS was overexpressed in epithelial tumor cells in 66% of the MBC samples versus 26% of normal samples (p= 1.40 × 10-7). Such positive MARCKS expression in epithelial tumor cells was associated with positive HER2 status (p= 4.0 × 10-3). It was associated with shorter OS in uni-and multivariate analysis. By contrast, stromal IHC MARCKS expression was correlated only with tumor grade. Conclusion: MARCKS tumor cell overexpression might in part explain the aggressiveness and the poor prognosis of MBC. MARCKS can represent a potential therapeutic target for MBC.
MeSH term(s)	Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms, Male/genetics ; Breast Neoplasms, Male/metabolism ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; Myristoylated Alanine-Rich C Kinase Substrate/biosynthesis ; Myristoylated Alanine-Rich C Kinase Substrate/genetics ; Myristoylated Alanine-Rich C Kinase Substrate/metabolism ; Prognosis ; Receptor, ErbB-2/genetics ; Receptor, ErbB-2/metabolism ; Retrospective Studies ; Survival Rate
Chemical Substances	MARCKS protein, human ; Myristoylated Alanine-Rich C Kinase Substrate (125267-21-2) ; ERBB2 protein, human (EC 2.7.10.1) ; Receptor, ErbB-2 (EC 2.7.10.1)
Language	English
Publishing date	2019-11-23
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2203517-5
ISSN	1875-8592 ; 1574-0153 ; 1875-8592
ISSN (online)	1875-8592 ; 1574-0153
ISSN	1875-8592
DOI	10.3233/CBM-190637
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Zs.A 6127: Show issues

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Article ; Online: CD8

Cellular & molecular immunology

2023 Volume 20, Issue 4, Page(s) 365–378

Abstract: CD226 has been reported to participate in the rescue of ... ...

Abstract	CD226 has been reported to participate in the rescue of CD8
MeSH term(s)	Humans ; CD8-Positive T-Lymphocytes ; Colorectal Neoplasms/pathology ; Liver Neoplasms/secondary ; Prognosis ; Receptors, Immunologic/metabolism ; Tumor Microenvironment
Chemical Substances	Receptors, Immunologic
Language	English
Publishing date	2023-01-30
Publishing country	China
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2435097-7
ISSN	2042-0226 ; 1672-7681
ISSN (online)	2042-0226
ISSN	1672-7681
DOI	10.1038/s41423-023-00978-2
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Zs.A 6681: Show issues

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Article ; Online: Forkhead box M1 (FOXM1) expression predicts disease free survival and may mediate resistance to chemotherapy and hormonotherapy in male breast cancer.

Abdeljaoued, Syrine / Bettaieb, Lhem / Nasri, Meher / Adouni, Olfa / Goucha, Aida / Bouzaiene, Hatem / Boussen, Hamouda / Rahal, Khaled / Gamoudi, Amor

Breast disease

2018 Volume 37, Issue 3, Page(s) 109–114

Abstract: Background: Male breast cancer (MBC) is a rare and neglected disease. Prognostic and predictive factors in MBC are extrapoled from trials conducted on its female counterpart.: Objective: Since the relationship between the transcription factor ... ...

Abstract	Background: Male breast cancer (MBC) is a rare and neglected disease. Prognostic and predictive factors in MBC are extrapoled from trials conducted on its female counterpart. Objective: Since the relationship between the transcription factor Forkhead box M1 (FOXM1) expression and the clinical response to chemotherapy and hormonotherapy in MBC remains unknown, we sought to investigate the predictive value of FOXM1 in MBC. Methods: FOXM1 expression was assessed in 130 MBC cases. Clinical significance was analyzed by Kaplan Meier curves, log-rank test and multivariate Cox regression analyses. Results: Patients with high FOXM1 expression had a significantly lower response rate to chemotherapy (P = 0.045) and hormonotherapy (P = 0.029) than those with low FOXM1 expression. Multivariate analyses indicated that FOXM1 was an independent prognostic factor for disease free survival in MBC patients (P < 0.001). Conclusions: FOXM1 may have a reliable predictive significance in male breast cancer and thus may become an important target for male breast cancer therapy in the near future.
MeSH term(s)	Adult ; Aged ; Aged, 80 and over ; Antineoplastic Agents/therapeutic use ; Antineoplastic Agents, Hormonal/therapeutic use ; Biomarkers, Tumor/genetics ; Biomarkers, Tumor/metabolism ; Breast Neoplasms, Male/drug therapy ; Breast Neoplasms, Male/genetics ; Breast Neoplasms, Male/pathology ; Breast Neoplasms, Male/surgery ; Disease-Free Survival ; Drug Resistance, Neoplasm/genetics ; Forkhead Box Protein M1/genetics ; Forkhead Box Protein M1/metabolism ; Gene Expression Regulation, Neoplastic ; Genetic Association Studies ; Humans ; Kaplan-Meier Estimate ; Male ; Middle Aged ; Prognosis ; Tamoxifen/therapeutic use ; Tunisia
Chemical Substances	Antineoplastic Agents ; Antineoplastic Agents, Hormonal ; Biomarkers, Tumor ; FOXM1 protein, human ; Forkhead Box Protein M1 ; Tamoxifen (094ZI81Y45)
Language	English
Publishing date	2018-04-10
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	639267-2
ISSN	1558-1551 ; 0888-6008
ISSN (online)	1558-1551
ISSN	0888-6008
DOI	10.3233/BD-170315
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Zs.A 2294: Show issues

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Article: Prognostic implications of the intrinsic molecular subtypes in male breast cancer.

Abdeljaoued, Syrine / Lhem, Bettaieb / Nasri, Meher / Adouni, Olfa / Goucha, Goucha Aida / Bouzaiene, Hatem / Boussen, Hamouda / Rahal, Rahal Khaled / Gamoudi, Gamoudi Amor

Journal of B.U.ON. : official journal of the Balkan Union of Oncology

2017 Volume 22, Issue 2, Page(s) 377–382

Abstract: Purpose: Intrinsic molecular subtyping has been widely used in female breast cancer, and it has proven its significance. In this article, we aimed to study the intrinsic subtypes of male breast cancer (MBC) in correlation with clinicopathological ... ...

Abstract	Purpose: Intrinsic molecular subtyping has been widely used in female breast cancer, and it has proven its significance. In this article, we aimed to study the intrinsic subtypes of male breast cancer (MBC) in correlation with clinicopathological features. Methods: We retrospectively identified 130 MBC cases from 2004 to 2013. Intrinsic molecular subtypes were determined by immunohistochemistry (IHC). Results: From a total of 130 MBC cases, 45.4% of tumors were luminal A subtype, 44.6% were luminal B, 5% were HER2 positive and 5% were triple negative tumors. There were statistically significant differences between different IHC intrinsic subtypes regarding tumor size (p=0.001), estrogen receptor (ER) status (p=0.001), progesterone receptor (PR) status (p=0.001), HER2 status (p=0.001) and Ki67 proliferation index (p=0.001). Conclusion: The distribution of breast cancer intrinsic subtypes in males is different compared to its female counterpart; however, they don't seem to give the same prognostic value.
MeSH term(s)	Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/metabolism ; Breast Neoplasms, Male/metabolism ; Breast Neoplasms, Male/pathology ; Humans ; Immunohistochemistry/methods ; Male ; Middle Aged ; Prognosis ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Retrospective Studies
Chemical Substances	Biomarkers, Tumor ; Receptors, Estrogen ; Receptors, Progesterone ; Receptor, ErbB-2 (EC 2.7.10.1)
Language	English
Publishing date	2017-04-05
Publishing country	Greece
Document type	Journal Article
ZDB-ID	2040386-0
ISSN	2241-6293 ; 1107-0625
ISSN (online)	2241-6293
ISSN	1107-0625
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Zs.A 5438: Show issues

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Article ; Online: Overexpression of FOXM1 Is a Potential Prognostic Marker in Male Breast Cancer.

Abdeljaoued, Syrine / Bettaieb, Ilhem / Nasri, Meher / Adouni, Olfa / Goucha, Aida / El Amine, Olfa / Boussen, Hammouda / Rahal, Khaled / Gamoudi, Amor

Oncology research and treatment

2017 Volume 40, Issue 4, Page(s) 167–172

Abstract: Background: Several studies have outlined biological differences between female and male breast cancer (MBC) and concluded that MBC should be considered as an entirely separate disease. Whether FOXM1 has any indication for prognosis in MBC patients ... ...

Abstract	Background: Several studies have outlined biological differences between female and male breast cancer (MBC) and concluded that MBC should be considered as an entirely separate disease. Whether FOXM1 has any indication for prognosis in MBC patients remains unknown. We sought to examine the expression levels of FOXM1 in MBC and to identify the relationship between FOXM1 expression and patient survival. Patients and methods: FOXM1 expression was evaluated in a total of 130 MBC specimens. Results: FOXM1 was overexpressed in 37% of the MBC samples. FOXM1 overexpression was significantly associated with tumor size (p = 0.045), histological grade (p = 0.048), lymph node metastasis (p = 0.012), Ki-67 proliferation index (p = 0.016), and molecular subtypes (p < 0.001). Multivariate analyses indicated that FOXM1 was an independent prognostic factor for overall survival in MBC patients (p < 0.001, hazard ratio = 0.69 (0.43-0.96)). Conclusions: Overexpression of FOXM1 was associated with well-established markers of poor prognosis; thus FOXM1 may represent a potential novel prognostic marker for MBC.
MeSH term(s)	Adult ; Age Distribution ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/metabolism ; Breast Neoplasms, Male/metabolism ; Breast Neoplasms, Male/mortality ; Breast Neoplasms, Male/pathology ; Forkhead Box Protein M1/metabolism ; Humans ; Male ; Middle Aged ; Prevalence ; Prognosis ; Reproducibility of Results ; Risk Factors ; Sensitivity and Specificity ; Survival Rate ; Tunisia/epidemiology ; Up-Regulation
Chemical Substances	Biomarkers, Tumor ; FOXM1 protein, human ; Forkhead Box Protein M1
Language	English
Publishing date	2017
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2760274-6
ISSN	2296-5262 ; 2296-5270
ISSN (online)	2296-5262
ISSN	2296-5270
DOI	10.1159/000458156
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Zs.A 1414: Show issues

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