Mechanisms of tumor immunotherapy, with a focus on thoracic cancers

If immunotherapy is currently considered as a valid treatment strategy in oncology, the concept that cancer could be cured by the mere manipulation of the immune system was almost inconceivable until few years ago, particularly in lung cancer. The use of immune checkpoint inhibitors has instead demonstrated to mediate significant long-term disease control so to rapidly enter clinical practice and represent the basis for most of the combination approaches under development. In light of the revolutionary results achieved through the pivotal clinical trials and the large expectations about the possibility to further improve clinical benefit and discover novel therapeutic targets, it is becoming nowadays mandatory to increase our knowledge on the basics of immunology in lung cancer. Defining the pathways that rule the interactions between tumor and immune cells and the requirements to achieve full-fledged immune responses able to mediate meaningful antitumor activity are present goals of the research ongoing worldwide. This knowledge would not only foster a more scientifically-based clinical development of novel drugs and combinations, but also provide valid biomarkers for patient selection and monitoring. In the present review we will address the available information about the immunological features of lung cancer, the backgrounds to the use of immunotherapeutics, the possible mechanisms underlying resistance and the strategies to improve immune-mediated tumor control. In doing this, we will be following the path traced in melanoma, the tumor histotype that taught us most of what we know about cancer immunotherapy.