%0 Journal Article
%T Multi-omic profiling reveals the endogenous and neoplastic responses to immunotherapies in cutaneous T cell lymphoma.
%A Glass DR
%A Mayer-Blackwell K
%A Ramchurren N
%A Parks KR
%A Duran GE
%A Wright AK
%A Bastidas Torres AN
%A Islas L
%A Kim YH
%A Fling SP
%A Khodadoust MS
%A Newell EW
%J Cell Rep Med
%V 5
%N 5
%D 2024 May 21
%M 38670099
%F 16.988
%R 10.1016/j.xcrm.2024.101527
%X Cutaneous T cell lymphomas (CTCLs) are skin cancers with poor survival rates and limited treatments. While immunotherapies have shown some efficacy, the immunological consequences of administering immune-activating agents to CTCL patients have not been systematically characterized. We apply a suite of high-dimensional technologies to investigate the local, cellular, and systemic responses in CTCL patients receiving either mono- or combination anti-PD-1 plus interferon-gamma (IFN-γ) therapy. Neoplastic T cells display no evidence of activation after immunotherapy. IFN-γ induces muted endogenous immunological responses, while anti-PD-1 elicits broader changes, including increased abundance of CLA+CD39+ T cells. We develop an unbiased multi-omic profiling approach enabling discovery of immune modules stratifying patients. We identify an enrichment of activated regulatory CLA+CD39+ T cells in non-responders and activated cytotoxic CLA+CD39+ T cells in leukemic patients. Our results provide insights into the effects of immunotherapy in CTCL patients and a generalizable framework for multi-omic analysis of clinical trials.