4.7 Article

Distinct Immune Gene Programs Associated with Host Tumor Immunity, Neoadjuvant Chemotherapy, and Chemoimmunotherapy in Resectable NSCLC

Journal

CLINICAL CANCER RESEARCH
Volume 28, Issue 11, Pages 2461-2473

Publisher

AMER ASSOC CANCER RESEARCH
DOI: 10.1158/1078-0432.CCR-21-3207

Keywords

-

Categories

Funding

  1. University of Texas Lung Specialized Programs of Research Excellence (SPORE) grant from the NCI [P50CA70907]
  2. NCI Cancer Center Support Grant [P30CA016672]
  3. Cancer Prevention and Research Institute of Texas [RP160668]
  4. NCI [U24CA224285]
  5. SEOM (Sociedad Espanola de Oncologia Medica)

Ask authors/readers for more resources

This study explores immune gene programs related to tumor immunity and response to neoadjuvant chemotherapy and chemoimmunotherapy in resectable NSCLC. The findings highlight the importance of specific immune signatures and pathways in predicting treatment response.
Purpose: Our understanding of the immunopathology of resect-able 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 per-formed in localized NSCLCs from three cohorts based on treatment: naive (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.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.7
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

No Data Available
No Data Available