Extending the immune phenotypes of lung cancer: Oasis in the desert

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Extending the immune phenotypes of lung cancer: Oasis in the desert

Backman, Max (author): Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden

La Fleur, Linnea (author): Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden

Kurppa, Pinja (author): Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden

Djureinovic, Dijana (author): Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden

Elfving, Hedvig (author): Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden

Brunnström, Hans (author): Division of Pathology, Lund University, Skåne University Hospital, Lund, Sweden

Mattsson, Johanna Sofia Margareta, 1985- (author): Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden

Pontén, Victor (author): Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden

Eltahir, Mohamed (author): Department of Pharmaceutical Bioscience, Uppsala University, Uppsala, Sweden

Mangsbo, Sara, 1981- (author): Department of Pharmaceutical Bioscience, Uppsala University, Uppsala, Sweden

Isaksson, Johan (author): Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden; Dept. of Respiratory Medicine, Gävle Hospital, Gävle, Sweden.

Jirström, Karin (author): Division of Pathology, Lund University, Skåne University Hospital, Lund, Sweden

Kärre, Klas (author): Department of Microbiology, Cell and Tumor Biology (MTC), Karolinska Institutet, Stockholm, Sweden.

Carbone, Ennio (author): Department of Microbiology, Cell and Tumor Biology (MTC), Karolinska Institutet, Stockholm, Sweden; Tumor Immunology and Immunopathology Laboratory, Dept. of Experimental and Clinical Medicine, University Magna Graecia of Catanzaro, Catanzaro, Italy.

Leandersson, Karin (author): Cancer Immunology, Dept. of Translational Medicine, Lund University, Skånes University Hospital, Malmö, Sweden

Mezheyeuski, Artur (author): Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden

Pontén, Fredrik (author): Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden

Lindskog, Cecilia (author): Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden

Botling, Johan (author): Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden

Micke, Patrick (author): Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden

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Introduction: Tumor infiltrating immune cells are key elements of the tumor microenvironment and mediate the anti-tumor effects of immunotherapy. The aim of the study was to characterize patterns of immune cell infiltration in non-small cell lung cancer (NSCLC) in relation to tumor mutations and clinicopathological parameters. Methods: Lymphocytes (CD4+, CD8+, CD20+, FOXP3+, CD45RO+), macrophages (CD163+), plasma cells (CD138+), NK cells (NKp46+) and PD-L1+ were annotated on a tissue microarray including 357 operated NSCLC cases. Somatic mutations and tumor mutational burden were analyzed by targeted sequencing for 82 genes, and transcriptomic immune patterns were established in 197 patients based on RNAseq data. Results: We identified somatic mutations (TP53, NF1, KEAP1, CSMD3, LRP1B) that correlated with specific immune cell infiltrates. Hierarchical clustering revealed four immune classes: with (1) high immune cell infiltration (“inflamed”), (2) low immune cell infiltration (“desert”), (3) a mixed phenotype, and (4) a new phenotype with an overall muted inflammatory cell pattern but with an imprint of NK and plasma cells. This latter class exhibited low expression of immune response-related genes (e.g. CXCL9, GZMB, INFG, TGFB1), but was linked to better survival and therefore designated “oasis”. Otherwise, the four immune classes were not related to the presence of specific mutations (EGFR, KRAS, TP53) or histologic subtypes. Conclusion: We present a compartment-specific immune cell analysis in the context of the molecular and clinical background of NSCLC and identified the novel immune class “oasis”. The immune classification helps to better define the immunogenic potency of NSCLC in the era of immunotherapy.

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Extending the immune phenotypes of lung cancer: Oasis in the desert

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