Different In Situ Immune Patterns between Primary Tumor and Lymph Node in Non-Small-Cell Lung Cancer: Potential Impact on Neoadjuvant Immunotherapy

Background. Neoadjuvant immunotherapy is promising for locally advanced non-small-cell lung cancer (NSCLC). The in situ immune patterns, as a predictor of PD-1/PD-L1 blockade outcomes, of the primary tumor (PT) and metastatic lymph nodes (mLNs) are unknown. Methods. Multiplex immunofluorescence stai...

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Main Authors: Zheng-Hao Ye, Hao Long, Ze-Rui Zhao
Format: Article
Language:English
Published: Wiley 2022-01-01
Series:Journal of Immunology Research
Online Access:http://dx.doi.org/10.1155/2022/8513747
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author Zheng-Hao Ye
Hao Long
Ze-Rui Zhao
author_facet Zheng-Hao Ye
Hao Long
Ze-Rui Zhao
author_sort Zheng-Hao Ye
collection DOAJ
description Background. Neoadjuvant immunotherapy is promising for locally advanced non-small-cell lung cancer (NSCLC). The in situ immune patterns, as a predictor of PD-1/PD-L1 blockade outcomes, of the primary tumor (PT) and metastatic lymph nodes (mLNs) are unknown. Methods. Multiplex immunofluorescence staining and multispectral imaging were used to evaluate the in situ immune patterns of T cells (CD3+) and cytotoxic T cells (CD8+) in terms of density, location (center of tumor (CT) and invasive margin (IM)), and the PD-L1 expression status of tumor cells and stromal T cells of paired PTs and mLNs in 38 stage III NSCLCs. Results. The densities of T cells and cytotoxic T cells were correlated between PTs and mLNs at both CT and IM. Higher densities of stromal T cells (S-CD3+) at CT and both S-CD3+ and cytotoxic T cells (S-CD8+) at IM were observed in mLNs compared to PTs, while in tumor compartment, there were no differences in the densities of T cells (T-CD3+) or cytotoxic T cells (T-CD8+). Only the density of stromal PD-L1-positive T cells (S-PD-L1+CD3+) at CT was correlated between PTs and mLNs, while the densities and frequencies of S-PD-L1+CD3+ at CT and IM of mLNs were higher than PTs. Combining positive score discordance of PD-L1 between PTs and mLNs was greater than tumor proportion score. Conclusions. In situ immune patterns of T cells and cytotoxic T cells were different between PTs and mLNs in NSCLC. The heterogeneity of the in situ immune patterns may result in different immune-mediated responses to neoadjuvant immunotherapy in PT and mLNs.
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spelling doaj-art-4045d3e0a9ca4ea0b1c035d22e072dda2025-02-03T01:22:58ZengWileyJournal of Immunology Research2314-71562022-01-01202210.1155/2022/8513747Different In Situ Immune Patterns between Primary Tumor and Lymph Node in Non-Small-Cell Lung Cancer: Potential Impact on Neoadjuvant ImmunotherapyZheng-Hao Ye0Hao Long1Ze-Rui Zhao2State Key Laboratory of Oncology in Southern ChinaState Key Laboratory of Oncology in Southern ChinaState Key Laboratory of Oncology in Southern ChinaBackground. Neoadjuvant immunotherapy is promising for locally advanced non-small-cell lung cancer (NSCLC). The in situ immune patterns, as a predictor of PD-1/PD-L1 blockade outcomes, of the primary tumor (PT) and metastatic lymph nodes (mLNs) are unknown. Methods. Multiplex immunofluorescence staining and multispectral imaging were used to evaluate the in situ immune patterns of T cells (CD3+) and cytotoxic T cells (CD8+) in terms of density, location (center of tumor (CT) and invasive margin (IM)), and the PD-L1 expression status of tumor cells and stromal T cells of paired PTs and mLNs in 38 stage III NSCLCs. Results. The densities of T cells and cytotoxic T cells were correlated between PTs and mLNs at both CT and IM. Higher densities of stromal T cells (S-CD3+) at CT and both S-CD3+ and cytotoxic T cells (S-CD8+) at IM were observed in mLNs compared to PTs, while in tumor compartment, there were no differences in the densities of T cells (T-CD3+) or cytotoxic T cells (T-CD8+). Only the density of stromal PD-L1-positive T cells (S-PD-L1+CD3+) at CT was correlated between PTs and mLNs, while the densities and frequencies of S-PD-L1+CD3+ at CT and IM of mLNs were higher than PTs. Combining positive score discordance of PD-L1 between PTs and mLNs was greater than tumor proportion score. Conclusions. In situ immune patterns of T cells and cytotoxic T cells were different between PTs and mLNs in NSCLC. The heterogeneity of the in situ immune patterns may result in different immune-mediated responses to neoadjuvant immunotherapy in PT and mLNs.http://dx.doi.org/10.1155/2022/8513747
spellingShingle Zheng-Hao Ye
Hao Long
Ze-Rui Zhao
Different In Situ Immune Patterns between Primary Tumor and Lymph Node in Non-Small-Cell Lung Cancer: Potential Impact on Neoadjuvant Immunotherapy
Journal of Immunology Research
title Different In Situ Immune Patterns between Primary Tumor and Lymph Node in Non-Small-Cell Lung Cancer: Potential Impact on Neoadjuvant Immunotherapy
title_full Different In Situ Immune Patterns between Primary Tumor and Lymph Node in Non-Small-Cell Lung Cancer: Potential Impact on Neoadjuvant Immunotherapy
title_fullStr Different In Situ Immune Patterns between Primary Tumor and Lymph Node in Non-Small-Cell Lung Cancer: Potential Impact on Neoadjuvant Immunotherapy
title_full_unstemmed Different In Situ Immune Patterns between Primary Tumor and Lymph Node in Non-Small-Cell Lung Cancer: Potential Impact on Neoadjuvant Immunotherapy
title_short Different In Situ Immune Patterns between Primary Tumor and Lymph Node in Non-Small-Cell Lung Cancer: Potential Impact on Neoadjuvant Immunotherapy
title_sort different in situ immune patterns between primary tumor and lymph node in non small cell lung cancer potential impact on neoadjuvant immunotherapy
url http://dx.doi.org/10.1155/2022/8513747
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AT haolong differentinsituimmunepatternsbetweenprimarytumorandlymphnodeinnonsmallcelllungcancerpotentialimpactonneoadjuvantimmunotherapy
AT zeruizhao differentinsituimmunepatternsbetweenprimarytumorandlymphnodeinnonsmallcelllungcancerpotentialimpactonneoadjuvantimmunotherapy