First published December 19, 2019 - More info
Anti-PD1 therapy has become an immunotherapeutic backbone for treating many cancer types. While many studies have aimed to characterize the immune response to anti-PD1 therapy in the tumor and in the peripheral blood, relatively less is known about the changes in the tumor draining lymph nodes (TDLNs). TDLNs are primary sites of tumor antigen exposure that are critical to both regulation and cross-priming of the antitumor immune response. We employed multi-panel mass cytometry to obtain a high-parameter proteomic (39 total unique markers) immune profile of the TDLN in a well-studied PD1-responsive immunocompetent mouse model. Based on combined hierarchal gating and unsupervised clustering analyses, we found that anti-PD1 therapy enhances remodeling of both B and T cell compartments toward memory phenotypes. Functionally, expression of checkpoint markers was increased in conjunction with production of IFNγ, TNFα, or IL2 in key cell types, including B and T cell subtypes and rarer subsets such as Tregs and NKT cells. A deeper profiling of the immunologic changes that occur in the TDLN milieu during effective anti-PD1 therapy may lead to the discovery of novel biomarkers for monitoring response and provide key insights toward developing combination immunotherapeutic strategies.