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Immune-checkpoint blockade is able to achieve durable responses in a subset of patients; however, we lack a satisfying comprehension of the underlying mechanisms of anti-CTLA-4- and anti-PD-1-induced tumor rejection. To address these issues, we utilized mass cytometry to comprehensively profile the effects of checkpoint blockade on tumor immune infiltrates in human melanoma and murine tumor models. These analyses reveal a spectrum of tumor-infiltrating T cell populations that are highly similar between tumor models and indicate that checkpoint blockade targets only specific subsets of tumor-infiltrating T cell populations. Anti-PD-1 predominantly induces the expansion of specific tumor-infiltrating exhausted-like CD8 T cell subsets. In contrast, anti-CTLA-4 induces the expansion of an ICOS+ Th1-like CD4 effector population in addition to engaging specific subsets of exhausted-like CD8 T cells. Thus, our findings indicate that anti-CTLA-4 and anti-PD-1 checkpoint-blockade-induced immune responses are driven by distinct cellular mechanisms.
Pubmed ID: 28803728 RIS Download
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Sequence analysis software for rt-qPCR analysis. It establishes standard curves, calculates delta delta Ct and automatically determines the ideal threshold setting for each run.
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Mus musculus with name B6.SJL-Ptprca Pepc
Mus musculus with name C57BL/6J from IMSR.
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View all literature mentionsCell line MC-38 is a Cancer cell line with a species of origin Mus musculus
View all literature mentionsCell line B16-BL6 is a Cancer cell line with a species of origin Mus musculus (Mouse)
View all literature mentionsThe SciCrunch Infrastructure was developed as a cooperative data platform to be used by diverse communities in making data more FAIR.
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