Current methods for biomarker discovery and target identification in immuno-oncology rely on static snapshots of tumor immunity. To thoroughly characterize the temporal nature of antitumor immune responses, we developed a 34-parameter spectral flow cytometry panel and performed high-throughput analyses in critical contexts. We leveraged two distinct preclinical models that recapitulate cancer immunoediting (NPK-C1) and immune checkpoint blockade (ICB) response (MC38), respectively, and profiled multiple relevant tissues at and around key inflection points of immune surveillance and escape and/or ICB response. Machine learning-driven data analysis revealed a pattern of KLRG1 expression that uniquely identified intratumoral effector CD4 T cell populations that constitutively associate with tumor burden across tumor models, and are lost in tumors undergoing regression in response to ICB. Similarly, a Helios KLRG1 subset of tumor-infiltrating regulatory T cells (Tregs) was associated with tumor progression from immune equilibrium to escape, and were also lost in tumors responding to ICB. Validation studies confirmed KLRG1 signatures in human tumorinfiltrating CD4 T cells associate with disease progression in renal cancer. These findings nominate KLRG1 CD4 T cell populations as subsets for further investigation in cancer immunity and demonstrate the utility of longitudinal spectral flow profiling as an engine of dynamic biomarker and/or target discovery.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9881861PMC
http://dx.doi.org/10.1101/2023.01.01.522340DOI Listing

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