TY - JOUR
T1 - Multipanel mass cytometry reveals anti–PD-1 therapy–mediated B and T cell compartment remodeling in tumor-draining lymph nodes
AU - Ho, Won Jin
AU - Yarchoan, Mark
AU - Charmsaz, Soren
AU - Munday, Rebecca M.
AU - Danilova, Ludmila
AU - Sztein, Marcelo B.
AU - Fertig, Elana J.
AU - Jaffee, Elizabeth M.
N1 - Funding Information:
receiving a commercial research grant from Bristol-Myers Squibb, Exelixis, and Merck & Co and is a consultant/ advisory board member for Eisai and Exelixis. EJF is a consultant for Champions Oncology. EMJ reports receiving a commercial research grant from Bristol-Myers Squibb, Aduro Biotech, and Amgen; has ownership interest (including stock, patents, etc.) in Aduro Biotech; and is a consultant/ advisory board member for CStone, Dragonfly, Genocea, and Adaptive Biotechnologies.
Funding Information:
WJH is the recipient of the American Society of Clinical Oncology Young Investigator Award and American Association of Cancer Research Incyte Immuno-Oncology Research Fellowship and is supported by NIH T32CA00971-38. The research is also supported by Hopkins-Allegheny Health Network Cancer Research Fund. The authors also thank Felix J. Hartmann and the Bendall lab for technical advice.
Publisher Copyright:
© 2020, American Society for Clinical Investigation.
PY - 2020/1/30
Y1 - 2020/1/30
N2 - Anti–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.
AB - Anti–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.
UR - http://www.scopus.com/inward/record.url?scp=85079557938&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85079557938&partnerID=8YFLogxK
U2 - 10.1172/jci.insight.132286
DO - 10.1172/jci.insight.132286
M3 - Article
C2 - 31855578
AN - SCOPUS:85079557938
SN - 2379-3708
VL - 5
JO - JCI Insight
JF - JCI Insight
IS - 2
M1 - e132286
ER -