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Tumor microenvironment disparity in multiple primary lung cancers: Impact of non-intrinsic factors, histological subtypes, and genetic aberrations.

Tumor microenvironment disparity in multiple primary lung cancers: Impact of non-intrinsic factors, histological subtypes, and genetic aberrations.

Authors :
Izumi M
Sawa K
Oyanagi J
Noura I
Fukui M
Ogawa K
Matsumoto Y
Tani Y
Suzumura T
Watanabe T
Kaneda H
Mitsuoka S
Asai K
Nishiyama N
Ohsawa M
Yamamoto N
Koh Y
Kawaguchi T
Source :
Translational oncology [Transl Oncol] 2021 Jul; Vol. 14 (7), pp. 101102. Date of Electronic Publication: 2021 Apr 27.
Publication Year :
2021

Abstract

Introduction: Multiple primary lung cancers (MPLCs) occur in common carcinogenetic risks such as lifestyle, biological aging, immune responses, hormones, and metabolism. Although MPLCs harbor various genetic profiles within the same individuals, differences in the tumor microenvironment (TME) are unclear. We investigated the impact of genetic aberrations, non-intrinsic factors, and pathological subtypes on tumor immunity.<br />Materials and Methods: In total, 73 surgically resected specimens from 32 patients with MPLC were analyzed. PD-L1 expression in tumor cells (TCs) and immune cells (ICs), CD3-positive tumor-infiltrating lymphocytes (TILs), CD8/CD3 ratios, and FOXP3-positive TILs that compose TMEs were evaluated by immunohistochemistry and classified on a score of 0-2. 38 tumors were sequenced for somatic mutations in 409 cancer-associated genes.<br />Results: Females and never or light smokers had a higher incidence of PD-L1-negative tumors and a higher concordance rate. PD-L1 positivity in TCs and ICs was significantly less frequent in EGFR-mutated than in wild-type tumors. Differences in the score of TMEs were observed between the KRAS-mutated-only tumor and the KRAS and TP53-co-mutated tumors, and between the KRAS-mutated-only tumor and the KRAS and STK11-co-mutated tumors. Significantly more FOXP3-high TILs were observed in invasive pathological subtypes than in non-invasive ones.<br />Conclusion: Comparing TMEs among MPLCs revealed that non-smokers or light smokers and females were unlikely to express PD-L1 regardless of tumor site and confirmed that the EGFR mutations and co-occurring KRAS and STK11 or TP53 mutations were associated with TME. Pathological subtypes may impact the efficacy of immune therapy due to their potential correlations with regulatory T cells.<br />Competing Interests: Declaration of Competing Interest Y. Koh has received honoraria from Thermo Fisher Scientific. All other authors declare that they have no competing interests.<br /> (Copyright © 2021. Published by Elsevier Inc.)

Details

Language :
English
ISSN :
1936-5233
Volume :
14
Issue :
7
Database :
MEDLINE
Journal :
Translational oncology
Publication Type :
Academic Journal
Accession number :
33930847
Full Text :
https://doi.org/10.1016/j.tranon.2021.101102