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Your search keyword '"Maldonado-Perez D"' showing total 2 results
Start Over Author "Maldonado-Perez D" Topic cd8-positive t-lymphocytes
2 results on '"Maldonado-Perez D"'

1. Self-Maintaining CD103 + Cancer-Specific T Cells Are Highly Energetic with Rapid Cytotoxic and Effector Responses.

Author

Abd Hamid M, Colin-York H, Khalid-Alham N, Browne M, Cerundolo L, Chen JL, Yao X, Rosendo-Machado S, Waugh C, Maldonado-Perez D, Bowes E, Verrill C, Cerundolo V, Conlon CP, Fritzsche M, Peng Y, and Dong T

Subjects
Antigens, CD immunology, Humans, Immunophenotyping methods, Integrin alpha Chains immunology, Lung Neoplasms metabolism, Lung Neoplasms pathology, Neoplasms metabolism, Neoplasms pathology, Prognosis, Receptors, Antigen, T-Cell genetics, Receptors, Antigen, T-Cell immunology, Transforming Growth Factor beta1 immunology, Transforming Growth Factor beta1 metabolism, Antigens, CD metabolism, CD8-Positive T-Lymphocytes immunology, Integrin alpha Chains metabolism, Lung Neoplasms immunology, Lymphocytes, Tumor-Infiltrating immunology, Neoplasms immunology, T-Lymphocytes, Cytotoxic immunology
Abstract

Enrichment of CD103 + tumor-infiltrating T lymphocytes (TIL) is associated with improved outcomes in patients. However, the characteristics of human CD103 + cytotoxic CD8 + T cells (CTL) and their role in tumor control remain unclear. We investigated the features and antitumor mechanisms of CD103 + CTLs by assessing T-cell receptor (TCR)-matched CD103 + and CD103 - cancer-specific CTL immunity in vitro and its immunophenotype ex vivo Interestingly, we found that differentiated CD103 + cancer-specific CTLs expressed the active form of TGFβ1 to continually self-regulate CD103 expression, without relying on external TGFβ1-producing cells. The presence of CD103 on CTLs improved TCR antigen sensitivity, which enabled faster cancer recognition and rapid antitumor cytotoxicity. These CD103 + CTLs had elevated energetic potential and faster migration capacity. However, they had increased inhibitory receptor coexpression and elevated T-cell apoptosis following prolonged cancer exposure. Our data provide fundamental insights into the properties of matured human CD103 + cancer-specific CTLs, which could have important implications for future designs of tissue-localized cancer immunotherapy strategies., (©2019 American Association for Cancer Research.)

Published
2020
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2. Enriched HLA-E and CD94/NKG2A Interaction Limits Antitumor CD8 + Tumor-Infiltrating T Lymphocyte Responses.

Author

Abd Hamid M, Wang RZ, Yao X, Fan P, Li X, Chang XM, Feng Y, Jones S, Maldonado-Perez D, Waugh C, Verrill C, Simmons A, Cerundolo V, McMichael A, Conlon C, Wang X, Peng Y, and Dong T

Subjects
Antigens, CD genetics, Antigens, CD metabolism, CD8-Positive T-Lymphocytes pathology, Cell Line, Tumor, Cytokines metabolism, Flow Cytometry, Gene Expression, Histocompatibility Antigens Class I genetics, Humans, Integrin alpha Chains genetics, Integrin alpha Chains metabolism, Ligands, Lymphocytes, Tumor-Infiltrating pathology, Tumor Microenvironment immunology, HLA-E Antigens, CD8-Positive T-Lymphocytes immunology, CD8-Positive T-Lymphocytes metabolism, Histocompatibility Antigens Class I immunology, Lymphocytes, Tumor-Infiltrating immunology, Lymphocytes, Tumor-Infiltrating metabolism, NK Cell Lectin-Like Receptor Subfamily C metabolism, NK Cell Lectin-Like Receptor Subfamily D metabolism
Abstract

Immunotherapy treatments with anti-PD-1 boost recovery in less than 30% of treated cancer patients, indicating the complexity of the tumor microenvironment. Expression of HLA-E is linked to poor clinical outcomes in mice and human patients. However, the contributions to immune evasion of HLA-E, a ligand for the inhibitory CD94/NKG2A receptor, when expressed on tumors, compared with adjacent tissue and peripheral blood mononuclear cells, remains unclear. In this study, we report that epithelial-derived cancer cells, tumor macrophages, and CD141 + conventional dendritic cells (cDC) contributed to HLA-E enrichment in carcinomas. Different cancer types showed a similar pattern of enrichment. Enrichment correlated to NKG2A upregulation on CD8 + tumor-infiltrating T lymphocytes (TIL) but not on CD4 + TILs. CD94/NKG2A is exclusively expressed on PD-1 high TILs while lacking intratumoral CD103 expression. We also found that the presence of CD94/NKG2A on human tumor-specific T cells impairs IL2 receptor-dependent proliferation, which affects IFNγ-mediated responses and antitumor cytotoxicity. These functionalities recover following antibody-mediated blockade in vitro and ex vivo Our results suggest that enriched HLA-E:CD94/NKG2A inhibitory interaction can impair survival of PD-1 high TILs in the tumor microenvironment., (©2019 American Association for Cancer Research.)

Published
2019
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