Blood Types as Tumor-Associated Carbohydrate Antigens That Determine the Efficacy of Immune Checkpoint Inhibitor Therapy in Lung Cancer

Immune checkpoint inhibitors, such as nivolumab and pembrozilumab, is a novel class of cancer treatment that have dramatically improved the clinical outcome of advanced lung cancer. However, these checkpoint inhibitors show clinical activity in only a limited number of patients. It is not known, what determines response to this form of therapy. Despite significant research efforts, current predictors of response to checkpoint inhibitors, such as PD1/PD-L1 staining (the molecular target of these therapeutic agents) or tumor mutation burden (the estimated number of tumor antigens eliciting immune response) have rather limited ability to support clinical decisions. We are proposing here a radical shift in our research focus from neoepitope peptide-based mechanisms to tumor associated carbohydrates (TACAs). Carbohydrates are a completely different, rather understudied class of tumor antigens. If this is indeed the case and in lung cancer tumor associated carbohydrate antigens also contribute to the efficacy to immune checkpoint inhibitor treatment, then our results will have a major impact both on the diagnostic and treatment strategy aspects of immune checkpoint inhibitor therapy. First, tumor associated carbohydrate antigens such as the aberrant expression of the Forssman antigen may produce a more accurate way to predict response to this treatment modality.