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

Autor: Nobuyuki Yamamoto, Yoko Tani, Jun Oyanagi, Tetsuya Watanabe, Koichi Ogawa, Ikue Noura, Yasuhiro Koh, Masahiko Ohsawa, Hiroyasu Kaneda, Kazuhisa Asai, Noritoshi Nishiyama, Mitsuru Fukui, Shigeki Mitsuoka, Tomoya Kawaguchi, Kenji Sawa, Motohiro Izumi, Tomohiro Suzumura, Yoshiya Matsumoto
Jazyk: angličtina
Rok vydání: 2021
Předmět:
0301 basic medicine
Cancer Research
Histology
ICI
immune checkpoint inhibitor
STK11
MPLC
multiple primary lung cancer
medicine.disease_cause
03 medical and health sciences
0302 clinical medicine
Immune system
Genetic aberration
NSCLC
non-small cell lung cancer
medicine
Non-intrinsic factor
TIL
tumor-infiltrating lymphocyte
Pathological
RC254-282
Original Research
TMB
tumor mutation burden
Tumor microenvironment
TC
tumor cell
business.industry
TME
tumor microenvironment
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
PD-1
programmed cell death-1
MIA
minimally invasive adenocarcinoma
NGS
next-generation sequencing
PD-L1
programmed death-ligand 1
030104 developmental biology
Oncology
030220 oncology & carcinogenesis
IC
immune cell
Cancer research
AIS
adenocarcinoma in situ
Immunohistochemistry
KRAS
Multiple primary lung cancer
business
CD8
Zdroj: Translational Oncology, Vol 14, Iss 7, Pp 101102-(2021)
Translational Oncology
ISSN: 1936-5233
Popis: Highlights • Tumor microenvironment (TME) was compared among multiple primary lung cancers (MPLCs). • Sex and smoking status concomitantly impacted PD-L1 expression in paired tumors. • EGFR mutations were independently associated with PD-L1 expression. • KRAS mutations altered the TMEs according to the types of co-mutations. • The number of FOXP3-positive t cells reflected histological subtypes.
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. 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. 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. 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.
Databáze: OpenAIRE
Externí odkaz: