Staring at the onco-exaptation: the two-faced medley of an ancient retrovirus, HERVH

Abstract

Communication between cancer cells and antitumor immune responsesEscaping senescence is thought to be a necessary step in cancer initiation (1). However, senescence is a double-edged sword, as this cellular stage is associated with the senescence-associated secretory phenotype (SASP), characterized by activated chemokine-signaling pathways (2) that correlate with neutrophil infiltration and worse prognosis. Lung squamous cell carcinoma (LUSC) is a type of lung cancer that persists globally among the main causes of cancer-related death in the world. The classical therapy for LUSC patients includes surgical removal of carcinomas, followed by radiotherapy and/ or chemotherapy (3). A more personalized therapy utilizes a tailored approach by inhibiting molecular pathways that target patient-specific driver mutations, which in LUSC are restricted to only two oncogenes (NTRK, MET), whereas in other lung cancers, a larger number of target oncogenes are known (3). Recently, immune checkpoint inhibitors (ICIs) have been used to activate the immune systems of patients to destroy tumor cells (4). Despite the considerable potential of immune treatments, only approximately 20% of patients respond to them (3), urging a better understanding of cellular heterogeneity and communication between cancer cells and antitumor immune responses.