Multi-omics Analysis Reveals Immune Features Associated with Immunotherapy Benefit in Patients with Squamous Cell Lung Cancer from Phase III Lung-MAP S1400I Trial.

Autor:	Parra ER; Departments of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas., Zhang J; Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas., Duose DY; Departments of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas., Gonzalez-Kozlova E; Department of Oncological Sciences, Mount Sinai, New York, New York.; Tisch Cancer Institute, Mount Sinai, New York, New York.; Precision Immunology Institute, Mount Sinai, New York, New York.; Icahn School of Medicine at Mount Sinai, New York, New York., Redman MW; SWOG Statistical Center, Fred Hutchinson Cancer Center, Seattle, Washington., Chen H; Department of Thoracic-Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas., Manyam GC; Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas., Kumar G; Departments of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas., Zhang J; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas., Song X; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas., Lazcano R; Departments of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas., Marques-Piubelli ML; Departments of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas., Laberiano-Fernandez C; Departments of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas., Rojas F; Departments of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas., Zhang B; Departments of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas., Taing L; CIMAC-CIDC Network, Pipeline Development and Portal Integration, Dana-Farber Cancer Institute, Boston, Massachusetts., Jhaveri A; CIMAC-CIDC Network, Pipeline Development and Portal Integration, Dana-Farber Cancer Institute, Boston, Massachusetts., Geisberg J; CIMAC-CIDC Network, Pipeline Development and Portal Integration, Dana-Farber Cancer Institute, Boston, Massachusetts., Altreuter J; CIMAC-CIDC Network, Pipeline Development and Portal Integration, Dana-Farber Cancer Institute, Boston, Massachusetts., Michor F; CIMAC-CIDC Network, Pipeline Development and Portal Integration, Dana-Farber Cancer Institute, Boston, Massachusetts., Provencher J; CIMAC-CIDC Network, Pipeline Development and Portal Integration, Dana-Farber Cancer Institute, Boston, Massachusetts., Yu J; CIMAC-CIDC Network, Pipeline Development and Portal Integration, Dana-Farber Cancer Institute, Boston, Massachusetts., Cerami E; CIMAC-CIDC Network, Pipeline Development and Portal Integration, Dana-Farber Cancer Institute, Boston, Massachusetts., Moravec R; Cancer Diagnosis Program, Division of Cancer Treatment and Diagnosis, NCI, Bethesda, Maryland., Kannan K; Departments of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas., Luthra R; Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas., Alatrash G; Department of Stem Cell Transplantation, The University of Texas MD Anderson Cancer, Houston, Texas., Huang HH; Precision Immunology Institute, Mount Sinai, New York, New York.; Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, New York., Xie H; Precision Immunology Institute, Mount Sinai, New York, New York., Patel M; Precision Immunology Institute, Mount Sinai, New York, New York., Nie K; Precision Immunology Institute, Mount Sinai, New York, New York., Harris J; Precision Immunology Institute, Mount Sinai, New York, New York., Argueta K; Precision Immunology Institute, Mount Sinai, New York, New York., Lindsay J; Department of Data Science, Dana-Farber Cancer Institute, Boston, Massachusetts., Biswas R; Department of Data Science, Dana-Farber Cancer Institute, Boston, Massachusetts., Van Nostrand S; CIMAC-CIDC Network, Pipeline Development and Portal Integration, Dana-Farber Cancer Institute, Boston, Massachusetts.; Department of Data Science, Dana-Farber Cancer Institute, Boston, Massachusetts., Kim-Schulze S; Department of Oncological Sciences, Mount Sinai, New York, New York.; Tisch Cancer Institute, Mount Sinai, New York, New York.; Precision Immunology Institute, Mount Sinai, New York, New York.; Icahn School of Medicine at Mount Sinai, New York, New York., Gray JE; Moffitt Cancer Caner, Tampa, Florida., Herbst RS; Yale Cancer Center, Yale School of Medicine, New Haven, Connecticut., Wistuba II; Departments of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas., Gettinger S; Moffitt Cancer Caner, Tampa, Florida., Kelly K; International Association for the Study of Lung Cancer, Denver, Colorado., Bazhenova L; University of California San Diego Moores Cancer Center, La Jolla, California., Gnjatic S; Department of Oncological Sciences, Mount Sinai, New York, New York.; Tisch Cancer Institute, Mount Sinai, New York, New York.; Precision Immunology Institute, Mount Sinai, New York, New York.; Icahn School of Medicine at Mount Sinai, New York, New York., Lee JJ; Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas., Zhang J; Department of Thoracic-Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas., Haymaker C; Departments of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Jazyk:	angličtina
Zdroj:	Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2024 Apr 15; Vol. 30 (8), pp. 1655-1668.
DOI:	10.1158/1078-0432.CCR-23-0251
Abstrakt:	Purpose: Identifying molecular and immune features to guide immune checkpoint inhibitor (ICI)-based regimens remains an unmet clinical need. Experimental Design: Tissue and longitudinal blood specimens from phase III trial S1400I in patients with metastatic squamous non-small cell carcinoma (SqNSCLC) treated with nivolumab monotherapy (nivo) or nivolumab plus ipilimumab (nivo+ipi) were subjected to multi-omics analyses including multiplex immunofluorescence (mIF), nCounter PanCancer Immune Profiling Panel, whole-exome sequencing, and Olink. Results: Higher immune scores from immune gene expression profiling or immune cell infiltration by mIF were associated with response to ICIs and improved survival, except regulatory T cells, which were associated with worse overall survival (OS) for patients receiving nivo+ipi. Immune cell density and closer proximity of CD8+GZB+ T cells to malignant cells were associated with superior progression-free survival and OS. The cold immune landscape of NSCLC was associated with a higher level of chromosomal copy-number variation (CNV) burden. Patients with LRP1B-mutant tumors had a shorter survival than patients with LRP1B-wild-type tumors. Olink assays revealed soluble proteins such as LAMP3 increased in responders while IL6 and CXCL13 increased in nonresponders. Upregulation of serum CXCL13, MMP12, CSF-1, and IL8 were associated with worse survival before radiologic progression. Conclusions: The frequency, distribution, and clustering of immune cells relative to malignant ones can impact ICI efficacy in patients with SqNSCLC. High CNV burden may contribute to the cold immune microenvironment. Soluble inflammation/immune-related proteins in the blood have the potential to monitor therapeutic benefit from ICI treatment in patients with SqNSCLC. (©2024 The Authors; Published by the American Association for Cancer Research.)
Databáze:	MEDLINE
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