Multipanel mass cytometry reveals anti-PD-1 therapy-mediated B and T cell compartment remodeling in tumor-draining lymph nodes
PublisherAmerican Society for Clinical Investigation
MetadataShow full item record
AbstractAnti-programmed cell death protein 1 (anti-PD-1) therapy has become an immunotherapeutic backbone for treating many cancer types. Although many studies have aimed to characterize the immune response to anti-PD-1 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 used multipanel mass cytometry to obtain a high-parameter proteomic (39 total unique markers) immune profile of the TDLNs in a well-studied PD-1-responsive, immunocompetent mouse model. Based on combined hierarchal gating and unsupervised clustering analyses, we found that anti-PD-1 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 IFN-γ, TNF-α, or IL-2 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-PD-1 therapy may lead to the discovery of novel biomarkers for monitoring response and provide key insights toward developing combination immunotherapeutic strategies.
SponsorsExelixis; Bristol-Myers Squibb, BMS; American Society of Clinical Oncology, ASCO; National Institutes of Health, NIH: T32CA00971-38
Keywordanti-programmed cell death protein 1
multipanel mass cytometry
Identifier to cite or link to this itemhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85079557938&doi=10.1172%2fjci.insight.132286&partnerID=40&md5=a2b926a59a2cbf0d18372861f645a103; http://hdl.handle.net/10713/12136