Moving Immune Checkpoint Blockade in Thoracic Tumors beyond NSCLC

Abstract

SCLC and malignant pleural mesothelioma (MPM) are historically characterized by a disappointing lack of significant therapeutic breakthroughs for novel agents, and both malignancies represent true unmet medical needs. Given the promising results of anti-cytotoxic T-lymphocyte associated protein-4 and anti-programmed cell death-1/programmed death ligand-1 antibodies in the treatment of advanced NSCLCs, these immune checkpoint inhibitors are now also under investigation in SCLC and MPM, as well as in thymic epithelial tumors (TETs). Here, we review the biological and clinical rationale for immune checkpoint inhibition in SCLC, MPM, and TETs and present preliminary clinical results with available antibodies. Immunotherapeutic perspectives for these malignancies in terms of novel agents currently under evaluation or anticipated in the near future are also discussed. Current immune checkpoint blockers targeting cytotoxic T-lymphocyte associated protein-4 and the programmed cell death-1/programmed death ligand-1 axis, administered alone or in combination and as multimodality treatment, are likely to be a valuable addition to the therapeutic array for managing SCLC and MPM; studies in TETs, which are currently in their infancy, are merited. Close attention to potential toxicities will be important to the success of such strategies in these settings.

Current WHO guidelines and the critical role of immunohistochemical markers in the subclassification of non-small cell lung carcinoma (NSCLC): Moving from targeted therapy to immunotherapy

“…More recently, immunotherapy has been developed and increasingly used in lung cancer patients. For example, PD-L1 (programmed cell death ligand 1) is a key immunoregulatory molecule which, upon interacting with its receptor, PD-1, inhibits the CD8 cytotoxic immune response and the resultant antitumor immune response [12–14]. In a variety of tumors, including lung cancer, PD-L1 is over expressed on tumor cells and plays an important role in the modulation of the immune response to both the tumor and host cells.…”

From targeting the tumor to targeting the immune system: Transversal challenges in oncology with the inhibition of the PD-1/PD-L1 axis

“…At the moment, only preliminary data have been published and CKI are currently under proposal for further investigations in this disease. Finally, early phases studies are ongoing to test CKI immunotherapy also in TETs[ 98 ].…”

The Potential Role of Cathepsin K in Non-Small Cell Lung Cancer

“…Since NSCLC remains asymptomatic during early stages, about 80% of patients are already in metastatic stages when they are diagnosed, and their 5-year survival rates are below 15% [ 2 ]. Despite recent progress in the development of novel medications and immunotherapies in treating NSCLC, the therapeutic efficacies still remain unsatisfactory [ 3 ]. Therefore, finding new therapeutic targets for the treatment of NSCLC has become a prioritized task [ 4 ].…”