The absence of HLA class I expression in non-small cell lung cancer correlates with the tumor tissue structure and the pattern of T cell infiltration

2016 ◽  
Vol 140 (4) ◽  
pp. 888-899 ◽  
Author(s):  
Francisco Perea ◽  
Mónica Bernal ◽  
Abel Sánchez-Palencia ◽  
Javier Carretero ◽  
Cristina Torres ◽  
...  
Keyword(s):  
Lung Cancer ◽  
T Cell ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Tumor Tissue ◽  
Hla Class I ◽  
Small Cell ◽  
Tissue Structure ◽  
Small Cell Lung ◽  
T Cell Infiltration

Association of a very high tumor mutational load with increased CD8+ and PD-1+ T-cell infiltration and improved clinical outcomes to PD-(L)1 blockade across different PD-L1 expression levels in non-small cell lung cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 9018-9018
Author(s):  
Biagio Ricciuti ◽  
Kathryn Cecilia Arbour ◽  
Joao Victor Machado Alessi ◽  
Navin Mahadevan ◽  
James Lindsay ◽  
...  
Keyword(s):  
Lung Cancer ◽  
T Cell ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Objective Response ◽  
Small Cell ◽  
Cell Infiltration ◽  
Small Cell Lung ◽  
T Cell Infiltration ◽  
Very High

9018 Background: Although high TMB correlates with improved outcomes to immune checkpoint inhibitors (ICI) in patients (pts) with non-small cell lung cancer (NSCLC), an optimal TMB cutoff to discriminate cancers most likely to respond to ICI has not been identified. Whether TMB impacts outcomes to ICI in different PD-L1 levels subgroups is also unclear. Methods: Unbiased recursive partitioning (URP) was used to identify an optimal TMB cutoff for objective response rate (ORR) in two independent cohorts of pts with NSCLC treated with ICI at DFCI and MSKCC. TCGA was interrogated to find differences in tumor immune cell subsets according to the TMB cutoff identified. Multiplexed immunofluorescence (IF) for CD8, PD-1, PD-L1, Foxp3, and CK7 was also performed on NSCLC samples at the DFCI. Results: In the DFCI (N=686) and MSKCC (N=672) cohorts, URP found an optimal TMB cutoff for ORR at 19 mutations/megabase (mut/Mb), corresponding to the ̃90th percentile in each cohort. Median progression-free (PFS) and overall survival (OS) were significantly longer in NSCLCs with TMB ≥19 mut/Mb vs <19 mut/Mb, in both cohorts (Table). After harmonizing TMB between DFCI OncoPanel and MSK-IMPACT NGS platforms, URP confirmed an optimal TMB cutoff for ORR at the 90th percentile in the combined cohort, which also associated with longer PFS/OS to ICI (Table). A TMB ≥90th percentile correlated with longer PFS/OS to ICI among NSCLCs with PD-L1 levels ≥50% and 1-49%, and longer PFS among those with PD-L1 <1% (Table). Cell subset transcriptome analysis from the TCGA showed higher proportions of CD8+ T cells (P=0.02) and M1 macrophages (P<0.01) among NSCLCs with a TMB ≥ vs <90th percentile. IF confirmed increased CD8+, CD8+ PD1+ T-cell infiltration (P<0.01), and increased CD8+/Foxp3+ ratio in NSCLC with very high TMB Conclusions: A very high TMB is associated with better outcomes to ICI and a distinct immunophenotype in NSCLC. Rational integration of TMB and PD-L1 expression may identify NSCLCs most likely to respond to ICI.[Table: see text]

Dynamic changes in PD-L1 expression and CD8+ T cell infiltration in non-small cell lung cancer following chemoradiation therapy

Lung Cancer ◽  
2019 ◽  
Vol 136 ◽  
pp. 30-36 ◽  
Author(s):  
Eun-Ah Choe ◽  
Yoon Jin Cha ◽  
Jae-Hwan Kim ◽  
Kyoung Ho Pyo ◽  
Min Hee Hong ◽  
...  
Keyword(s):  
Lung Cancer ◽  
T Cell ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Cd8 T Cell ◽  
Small Cell ◽  
Chemoradiation Therapy ◽  
Small Cell Lung ◽  
Dynamic Changes ◽  
T Cell Infiltration

scholarly journals Global analysis of shared T cell specificities in human non-small cell lung cancer enables HLA inference and antigen discovery

Immunity ◽  
2021 ◽  
Vol 54 (3) ◽  
pp. 586-602.e8
Author(s):  
Shin-Heng Chiou ◽  
Diane Tseng ◽  
Alexandre Reuben ◽  
Vamsee Mallajosyula ◽  
Irene S. Molina ◽  
...  
Keyword(s):  
Lung Cancer ◽  
T Cell ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Global Analysis ◽  
Small Cell ◽  
Small Cell Lung ◽  
Antigen Discovery
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