Dataset Information

Spatial Analysis and Clinical Significance of HLA Class-I and Class-II Subunit Expression in Non-Small Cell Lung Cancer.

ABSTRACT:

Purpose

To analyze the distribution, associated immune contexture, and clinical significance of human leukocyte antigen (HLA) class-I and HLA class-II subunits in non-small cell lung cancer (NSCLC).

Experimental design

Using spatially resolved and quantitative multiplexed immunofluorescence we studied the tumor/stromal tissue distribution, cancer cell-specific defects, and clinicopathologic/survival associations of β2 microglobulin (β2M), HLA-A, and HLA-B,-C heavy chains, as well as HLA class-II β chain in >700 immunotherapy-naïve NSCLCs from four independent cohorts. Genomic analysis of HLA genes in NSCLC was performed using two publicly available cohorts.

Results

Cancer cell-specific downregulation of HLA markers was identified in 30.4% of cases. β2M was downregulated in 9.8% (70/714), HLA-A in 9% (65/722), HLA-B,-C in 12.1% (87/719), and HLA class-II in 17.7% (127/717) of evaluable samples. Concurrent downregulation of β2M, HLA-B,-C, and HLA class-II was commonly identified. Deleterious mutations in HLA genes were detected in <5% of lung malignancies. Tumors with cancer cell-specific β2M downregulation displayed reduced T cells and increased natural killer (NK)-cell infiltration. Samples with cancer cell HLA-A downregulation displayed modest increase in CD8⁺ T cells and NK-cell infiltration. Samples with cancer cell-selective HLA-B,-C or HLA class-II downregulation displayed reduced T cells and NK-cell infiltration. There was limited association of the markers with clinicopathologic variables and KRAS/EGFR mutations. Cancer cell-selective downregulation of the HLA subunits was associated with shorter overall survival.

Conclusions

Our results reveal frequent and differential defects in HLA class-I and HLA class-II protein subunit expression in immunotherapy-naïve NSCLCs associated with distinct tumor microenvironment composition and patient survival.

SUBMITTER: Datar IJ

PROVIDER: S-EPMC8734284 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature

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Publications

Spatial Analysis and Clinical Significance of HLA Class-I and Class-II Subunit Expression in Non-Small Cell Lung Cancer.

Datar Ila J IJ Hauc Sacha C SC Desai Shruti S Gianino Nicole N Henick Brian B Liu Yuting Y Syrigos Kostas K Rimm David L DL Kavathas Paula P Ferrone Soldano S Schalper Kurt A KA

Clinical cancer research : an official journal of the American Association for Cancer Research 20210218 10

<h4>Purpose</h4>To analyze the distribution, associated immune contexture, and clinical significance of human leukocyte antigen (HLA) class-I and HLA class-II subunits in non-small cell lung cancer (NSCLC).<h4>Experimental design</h4>Using spatially resolved and quantitative multiplexed immunofluorescence we studied the tumor/stromal tissue distribution, cancer cell-specific defects, and clinicopathologic/survival associations of β2 microglobulin (β2M), HLA-A, and HLA-B,-C heavy chains, as well ...[more]

PMID: 33602682

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Project description:BackgroundAmrubicin chemotherapy is a treatment option for patients with non-small cell lung cancer (NSCLC) after third-line treatment in Japan. Although topoisomerase-II (Topo-II), a target of amrubicin, has been reported to be a prognostic or predictive marker for chemosensitivity and clinical outcomes in various types of malignancies, its effects in the Japanese population remain unknown.MethodsData regarding 44 patients with advanced NSCLC treated with amrubicin between April 2004 and May 2014 were retrospectively analyzed. We evaluated the expression levels of Topo-II by immunohistochemical staining of tumor specimens obtained via biopsy or surgical resection.ResultsThe majority of enrolled patients were men (68%) with a median age of 67 (range, 43-78) years. The most common histological type was adenocarcinoma (70%). High Topo-II expression was observed in 13 (30%) of the 44 patients. The median progression-free survival and overall survival (OS) durations were 1.8 and 8.8 months, respectively. While there was no significant association between Topo-II expression and progression-free survival, patients with low Topo-II expression had significantly longer OS than did those with high Topo-II expression. Good performance status and low expression of Topo-II were all significantly associated with a favorable OS.ConclusionLow expression of Topo-II was identified as an independent prognostic factor for longer survival in patients with NSCLC receiving amrubicin, a Topo-II inhibitor.Key pointsSignificant findings of the study The median progression-free survival and overall survival (OS) durations were 1.8 and 8.8 months, respectively. While there was no significant association between Topo-II expression and progression-free survival, patients with low Topo-II expression had significantly longer OS than did those with high Topo-II expression. Good performance status and low expression of Topo-II were all significantly associated with a favorable OS. What this study adds This study is the first to assess the effects of topoisomerase-II (Topo-II), a target of amrubicin, as a prognostic or predictive marker for chemosensitivity and clinical outcomes in the Japanese population.

Dataset Information

Spatial Analysis and Clinical Significance of HLA Class-I and Class-II Subunit Expression in Non-Small Cell Lung Cancer.

Purpose

Experimental design

Results

Conclusions

Publications

Spatial Analysis and Clinical Significance of HLA Class-I and Class-II Subunit Expression in Non-Small Cell Lung Cancer.

Similar Datasets

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