Faculty, Staff and Student Publications
Publication Date
6-1-2022
Journal
Clinical Cancer Research
Abstract
Purpose: Our understanding of the immunopathology of resectable non-small cell lung cancer (NSCLC) is still limited. Here, we explore immune programs that inform of tumor immunity and response to neoadjuvant chemotherapy and chemoimmunotherapy in localized NSCLC.
Experimental design: Targeted immune gene sequencing using the HTG Precision Immuno-Oncology panel was performed in localized NSCLCs from three cohorts based on treatment: naïve (n = 190), neoadjuvant chemotherapy (n = 38), and neoadjuvant chemoimmunotherapy (n = 21). Tumor immune microenvironment (TIME) phenotypes were based on the location of CD8+ T cells (inflamed, cold, excluded), tumoral PD-L1 expression (<1% and ≥1%), and tumor-infiltrating lymphocytes (TIL). Immune programs and signatures were statistically analyzed on the basis of tumoral PD-L1 expression, immune phenotypes, and pathologic response and were cross-compared across the three cohorts.
Results: PD-L1-positive tumors exhibited increased signature scores for various lymphoid and myeloid cell subsets (P < 0.05). TIME phenotypes exhibited disparate frequencies by stage, PD-L1 expression, and mutational burden. Inflamed and PD-L1+/TILs+ NSCLCs displayed overall significantly heightened levels of immune signatures, with the excluded group representing an intermediate state. A cytotoxic T-cell signature was associated with favorable survival in neoadjuvant chemotherapy-treated NSCLCs (P < 0.05). Pathologic response to chemoimmunotherapy was positively associated with higher expression of genes involved in immune activation, chemotaxis, as well as T and natural killer cells (P < 0.05 for all). Among the three cohorts, chemoimmunotherapy-treated NSCLCs exhibited the highest scores for various immune cell subsets including T effector and B cells (P < 0.05).
Conclusions: Our findings highlight immune gene programs that may underlie host tumor immunity and response to neoadjuvant chemotherapy and chemoimmunotherapy in resectable NSCLC.
Keywords
B7-H1 Antigen, Biomarkers, Tumor, CD8-Positive T-Lymphocytes, Carcinoma, Non-Small-Cell Lung, Humans, Immunotherapy, Lung Neoplasms, Lymphocytes, Tumor-Infiltrating, Neoadjuvant Therapy, Prognosis, Tumor Microenvironment, Early-stage NSCLC, immunopathology, immune gene profiling, neoadjuvant chemotherapy, neoadjuvant chemoimmunotherapy
DOI
10.1158/1078-0432.CCR-21-3207
PMID
35394499
PMCID
PMC9167789
PubMedCentral® Posted Date
12-1-2022
PubMedCentral® Full Text Version
Author MSS
Published Open-Access
yes
Included in
Bioinformatics Commons, Biomedical Informatics Commons, Genetic Phenomena Commons, Immunotherapy Commons, Medical Genetics Commons, Oncology Commons
