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Tumor Infiltrating Effector Memory Antigen-Specific CD8(+) T Cells Predict Response to Immune Checkpoint Therapy
Immune checkpoint therapy (ICT) results in durable responses in individuals with some cancers, but not all patients respond to treatment. ICT improves CD8(+) cytotoxic T lymphocyte (CTL) function, but changes in tumor antigen-specific CTLs post-ICT that correlate with successful responses have not b...
Autores principales: | , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7688517/ https://www.ncbi.nlm.nih.gov/pubmed/33262762 http://dx.doi.org/10.3389/fimmu.2020.584423 |
Sumario: | Immune checkpoint therapy (ICT) results in durable responses in individuals with some cancers, but not all patients respond to treatment. ICT improves CD8(+) cytotoxic T lymphocyte (CTL) function, but changes in tumor antigen-specific CTLs post-ICT that correlate with successful responses have not been well characterized. Here, we studied murine tumor models with dichotomous responses to ICT. We tracked tumor antigen-specific CTL frequencies and phenotype before and after ICT in responding and non-responding animals. Tumor antigen-specific CTLs increased within tumor and draining lymph nodes after ICT, and exhibited an effector memory-like phenotype, expressing IL-7R (CD127), KLRG1, T-bet, and granzyme B. Responding tumors exhibited higher infiltration of effector memory tumor antigen-specific CTLs, but lower frequencies of regulatory T cells compared to non-responders. Tumor antigen-specific CTLs persisted in responding animals and formed memory responses against tumor antigens. Our results suggest that increased effector memory tumor antigen-specific CTLs, in the presence of reduced immunosuppression within tumors is part of a successful ICT response. Temporal and nuanced analysis of T cell subsets provides a potential new source of immune based biomarkers for response to ICT. |
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