Since 2013, when anticancer immunotherapy became the breakthrough of the year, a growing body of evidence showed long-term disease control and overall survival improvement with immune checkpoint inhibitors (ICIs) compared with standard chemotherapy in several cancers. Anti-PD-1 and anti-PD-L1 drugs subverted the standard of treatment of non-small cell lung cancer (NSCLC). Some drugs came into clinical practice with different indications; as single agents or in combinations, and in PD-L1 selected and unselected patients. The efficacy of ICI in early-stage NSCLC, Small Cell Lung Cancer (SCLC), Malignant Pleural Mesothelioma (MPM) and Thymic Epithelial Tumors (TETs) is under active investigation. PD-L1 expression in cancer cells is not considered the only predictive marker of an immunogenic response to checkpoint inhibitors, its expression on tumor-infiltrating lymphocytes (TILs), tumor mutation burden, or immune-related genetic signatures are other predictors under investigation.

The role of PD-L1 expression and tumor immune microenvironment (TME) in oncogene-addicted NSCLC and the potential interplay between TME and genetic signatures of the tumor is still unclear.
Some reports evidenced tumor immune microenvironment interplay with cancer-related genetic alterations. KRAS mutations seem to confer an immunosuppressive phenotype in pancreatic ductal adenocarcinoma (PDAC) and NSCLC by increasing IL-10 secretion. Conversely, conflicting results have been reported about the role of EGFR mutations in NSCLC. EGFR mutation was associated with higher expression of PD-L1 compared to wild type tumors, but patients with mutant NSCLC did not benefit from ICIs as single agents. Based on these notions, a deeper understanding of the immune landscape related to the genetics of cancers might help both in the identification of reliable biomarkers for patient selection and in the identification of combined treatments able to target immune response at different levels.

In this Research Topic, we would like to discuss the current advances in the study of the interplay between the tumor immune microenvironment and genetic alterations in thoracic malignancies, such as NSCLC, SCLC, TETs, and MPM.

We welcome the submission of Original Research, Methods and Clinical Trials covering, but not limited, to the following subtopics:
● Tumor immune microenvironment in oncogene-addicted NSCLC
● Identification of immune-related genetic signatures in thoracic cancers
● Cancer-related genetic alterations and tumor immune microenvironment interplay in uncommon thoracic cancers
● Cancer-related genetic alteration and response to immunotherapy in thoracic cancers
● Tumor mutational burden in uncommon thoracic cancers and predictive value of ICIs response

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Frontiers in Oncology

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