TY - JOUR
T1 - Distinct Immune Gene Programs Associated with Host Tumor Immunity, Neoadjuvant Chemotherapy, and Chemoimmunotherapy in Resectable NSCLC
AU - Rocha, Pedro
AU - Zhang, Jiexin
AU - Laza-Briviesc, Raquel
AU - Cruz-Bermúde, Alberto
AU - Bota-Rabasseda, Neus
AU - Sanchez-Espirido, Beatriz
AU - Yoshimura, Katsuhiro
AU - Behrens, Carmen
AU - Lu, Wei
AU - Tang, Ximing
AU - Pataer, Apar
AU - Parra, Edwin R.
AU - Haymaker, Cara
AU - Fujimoto, Junya
AU - Swisher, Stephen G.
AU - Heymach, John V.
AU - Gibbons, Don L.
AU - Lee, J. Jack
AU - Sepesi, Boris
AU - Cascone, Tina
AU - Solis, Luisa M.
AU - Provencio, Mariano
AU - Wistuba, Ignacio I.
AU - Kadara, Humam
N1 - Publisher Copyright:
© 2022 American Association for Cancer Research.
PY - 2022/6/1
Y1 - 2022/6/1
N2 - 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, chemoimmunotherapytreated 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.
AB - 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, chemoimmunotherapytreated 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.
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U2 - 10.1158/1078-0432.CCR-21-3207
DO - 10.1158/1078-0432.CCR-21-3207
M3 - Article
C2 - 35394499
AN - SCOPUS:85131215557
SN - 1078-0432
VL - 28
SP - 2461
EP - 2473
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 11
ER -