Dataset Information

Cyclophosphamide treatment regulates the balance of functional/exhausted tumor-specific CD8⁺ T cells.

ABSTRACT: An important question is how chemotherapy may (re-)activate tumor-specific immunity. In this study, we provide a phenotypic, functional and genomic analysis of tumor-specific CD8⁺ T cells in tumor (P815)-bearing mice, treated or not with cyclophosphamide. Our data show that chemotherapy favors the development of effector-type lymphocytes in tumor bed, characterized by higher KLRG-1 expression, lower PD-1 expression and increased cytotoxicity. This suggests re-engagement of T lymphocytes into the effector program. IFN-I appears involved in this remodeling. Our findings provide some insight into how cyclophosphamide regulates the amplitude and quality of tumor-specific immune responses.

SUBMITTER: Hanoteau A

PROVIDER: S-EPMC5593741 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Cyclophosphamide treatment regulates the balance of functional/exhausted tumor-specific CD8<sup>+</sup> T cells.

Hanoteau Aurélie A Henin Coralie C Svec David D Bisilliat Donnet Charlotte C Denanglaire Sébastien S Colau Didier D Romero Pedro P Leo Oberdan O Van den Eynde Benoit B Moser Muriel M

Oncoimmunology 20170511 8

An important question is how chemotherapy may (re-)activate tumor-specific immunity. In this study, we provide a phenotypic, functional and genomic analysis of tumor-specific CD8<sup>+</sup> T cells in tumor (P815)-bearing mice, treated or not with cyclophosphamide. Our data show that chemotherapy favors the development of effector-type lymphocytes in tumor bed, characterized by higher KLRG-1 expression, lower PD-1 expression and increased cytotoxicity. This suggests re-engagement of T lymphocyt ...[more]

PMID: 28919989

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Project description:CD8+ cytotoxic T lymphocytes (CTLs) exert potent antiviral activity after HIV/SIV infection. However, efforts to harness the antiviral efficacy of CTLs for HIV/SIV prophylaxis and therapy have been severely hindered by two major problems: viral escape and exhaustion. By contrast, CTLs directed against human cytomegalovirus (HCMV), a ubiquitous chronic herpesvirus, seldom select for escape mutations and remain functional and refractory to exhaustion during chronic HCMV and HIV infection. Recently, attempts have been made to retarget HCMV-specific CTLs for cancer immunotherapy. We speculate that such a strategy may also be beneficial in the context of HIV/SIV infection, facilitating CTL-mediated control of HIV/SIV replication. As a preliminary assessment of the validity of this approach, we investigated the phenotypes and functionality of rhesus CMV (RhCMV)-specific CTLs in SIVmac239-infected Indian rhesus macaques (RMs), a crucial HIV animal model system. We recently identified two immunodominant, Mamu-A∗02-restricted CTL epitopes derived from RhCMV proteins and sought to evaluate the phenotypic and functional characteristics of these CTL populations in chronic SIVmac239 infection. We analyzed and directly compared RhCMV- and SIVmac239-specific CTLs during SIVmac239 infection in a cohort of Mamu-A∗01 + and Mamu-A∗02 + RMs. CTL populations specific for at least one of the RhCMV-derived CTL epitopes were detected in ten of eleven Mamu-A∗02 + animals tested, and both populations were detected in five of these animals. Neither RhCMV-specific CTL population exhibited significant changes in frequency, memory phenotype, granzyme B expression, exhaustion marker (PD-1 and CTLA-4) expression, or polyfunctionality between pre- and chronic SIVmac239 infection timepoints. In chronic SIVmac239 infection, RhCMV-specific CTLs exhibited higher levels of granzyme B expression and polyfunctionality, and lower levels of exhaustion marker expression, than SIVmac239-specific CTLs. Additionally, compared to SIVmac239-specific CTLs, greater proportions of RhCMV-specific CTLs were of the terminally differentiated effector memory phenotype (CD28- CCR7-) during chronic SIVmac239 infection. These results suggest that, in contrast to SIVmac239-specific CTLs, RhCMV-specific CTLs maintain their phenotypes and cytolytic effector functions during chronic SIVmac239 infection, and that retargeting RhCMV-specific CTLs might be a promising SIV immunotherapeutic strategy.

Dataset Information

Cyclophosphamide treatment regulates the balance of functional/exhausted tumor-specific CD8⁺ T cells.

Publications

Cyclophosphamide treatment regulates the balance of functional/exhausted tumor-specific CD8<sup>+</sup> T cells.

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Dataset Information

Cyclophosphamide treatment regulates the balance of functional/exhausted tumor-specific CD8+ T cells.

Publications

Cyclophosphamide treatment regulates the balance of functional/exhausted tumor-specific CD8<sup>+</sup> T cells.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Cyclophosphamide treatment regulates the balance of functional/exhausted tumor-specific CD8⁺ T cells.