Unknown

Dataset Information

0

Enhancement of tumor-reactive cytotoxic CD4+ T cell responses after ipilimumab treatment in four advanced melanoma patients.


ABSTRACT: CD4(+) T cells provide help to enhance and sustain cytotoxic CD8(+) T cell responses. A direct lytic role for this cell population in mouse models further supports the use of tumor-reactive CD4(+) T cells for cancer immunotherapy. CTLA-4 blockade has been shown to expand antigen-specific cytotoxic CD4(+) T cells in mouse models. We took advantage of spontaneous immunity to the NY-ESO-1 cancer-testis antigen to investigate quantitative and qualitative changes in antigen-specific CD4(+) T cell responses after ipilimumab (anti-CTLA-4 monoclonal antibody) treatment in advanced melanoma patients. Four NY-ESO-1 seropositive melanoma patients were chosen upon the availability of suitable blood specimens for characterizing the functions of NY-ESO-1 antigen-specific CD4(+) T cell response by enzyme-linked immunospot (ELISPOT), intracellular cytokine staining (ICS) and cytotoxicity assays. Multiple NY-ESO-1 antigen-specific CD4(+) T cell responses with Th1 dominance were induced or enhanced after ipilimumab treatment in peripheral blood in all four patients. NY-ESO-1 antigen-specific CD4(+) T cell lines established from all 4 patients after ipilimumab treatment recognized naturally processed NY-ESO-1 protein in antigen-presenting cells, expressed master transcription factor Eomesodermin (Eomes) and secreted perforin and Granzyme B. Finally, we demonstrated that these NY-ESO-1 antigen-specific CD4(+) T cell lines directly lysed autologous melanoma cell lines expressing NY-ESO-1 in an MHC class II restricted manner. Our results show that antigen specific cytotoxic CD4(+) T cell responses are induced after ipilimumab therapy in human cancer patients. Ipilimumab may induce the expression of lytic granules on antigen specific cytotoxic CD4(+) T cells via Eomes, revealing a novel consequence of immunologic checkpoint blockade.

SUBMITTER: Kitano S 

PROVIDER: S-EPMC3880021 | biostudies-literature | 2013 Oct

REPOSITORIES: biostudies-literature

altmetric image

Publications

Enhancement of tumor-reactive cytotoxic CD4+ T cell responses after ipilimumab treatment in four advanced melanoma patients.

Kitano Shigehisa S   Tsuji Takemasa T   Liu Caillian C   Hirschhorn-Cymerman Daniel D   Kyi Chrisann C   Mu Zhenyu Z   Allison James P JP   Gnjatic Sacha S   Yuan Jianda D JD   Wolchok Jedd D JD  

Cancer immunology research 20131001 4


CD4(+) T cells provide help to enhance and sustain cytotoxic CD8(+) T cell responses. A direct lytic role for this cell population in mouse models further supports the use of tumor-reactive CD4(+) T cells for cancer immunotherapy. CTLA-4 blockade has been shown to expand antigen-specific cytotoxic CD4(+) T cells in mouse models. We took advantage of spontaneous immunity to the NY-ESO-1 cancer-testis antigen to investigate quantitative and qualitative changes in antigen-specific CD4(+) T cell res  ...[more]

Similar Datasets

| S-EPMC2839156 | biostudies-literature
| S-EPMC5698004 | biostudies-literature
| S-EPMC8544022 | biostudies-literature
| S-EPMC6607934 | biostudies-literature
| S-EPMC2999944 | biostudies-literature
| S-EPMC6875707 | biostudies-literature
| S-EPMC5706778 | biostudies-literature
| S-EPMC9243303 | biostudies-literature
| S-EPMC3912016 | biostudies-literature
| S-EPMC8718224 | biostudies-literature