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Multipanel mass cytometry reveals anti–PD-1 therapy–mediated B and T cell compartment remodeling in tumor-draining lymph nodes
Won Jin Ho, … , Elana J. Fertig, Elizabeth M. Jaffee
Won Jin Ho, … , Elana J. Fertig, Elizabeth M. Jaffee
Published December 19, 2019
Citation Information: JCI Insight. 2020;5(2):e132286. https://doi.org/10.1172/jci.insight.132286.
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Research Article Immunology Oncology

Multipanel mass cytometry reveals anti–PD-1 therapy–mediated B and T cell compartment remodeling in tumor-draining lymph nodes

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Abstract

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.

Authors

Won Jin Ho, Mark Yarchoan, Soren Charmsaz, Rebecca M. Munday, Ludmila Danilova, Marcelo B. Sztein, Elana J. Fertig, Elizabeth M. Jaffee

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Figure 3

Unsupervised analysis of lymph node remodeling in the T cell compartment.

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Unsupervised analysis of lymph node remodeling in the T cell compartment...
(A) Based on the data set from 9 canonical markers in the T cell subtyping mass cytometry panel, FlowSOM algorithm was used to yield 20 metaclusters annotated into 10 final clusters. The resulting phenograph for all the samples in the data set is shown. (B) Number of cells per lymph node within each of the T cell clusters is shown for each individual mouse for all 3 groups. (C) Numbers of cells per lymph node for 5 key T cell clusters are summarized in scatter plots with mean ± SD (n = 5) for the 3 groups, non–tumor-bearing mice, isotype-treated mice, and anti–PD-1–treated mice. Results for repeated-measures ANOVA followed by pairwise testing are shown as FDR-adjusted *P ≤ 0.05. Breg, regulatory B cells; Imm, immature; Mat, mature.

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