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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 8

Functional analysis of the B cell compartment.

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Functional analysis of the B cell compartment.
(A) All the B cell cluste...
(A) All the B cell clusters are shown on the UMAP plot as a reference for other UMAP plots in the figure. Expression of PD-L1 (B) and CD40 (C) is visualized in aggregate data from all samples as heatmaps superimposed on the B cell cluster UMAP plot shown in A with quantitative scatter plots showing mean ± SD (n = 5) of non–tumor-bearing mouse lymph nodes, isotype-treated TDLNs, and anti–PD-1–treated TDLNs for (D) PD-L1 in transitional B2, memory B1, and memory B2 subtypes and for (E) CD40 in transitional B2 and memory B3 subtypes. Results for repeated-measures ANOVA followed by pairwise testing are shown as FDR-adjusted *P ≤ 0.05; ***P ≤ 0.005.

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