This specially commissioned text covers a range of topics relating to chemotherapy and the immune system.

Immunity, Cancer, and Chemotherapy focuses on the interference of drugs on antibody response and transplantation immunity. The selection first offers information on the effects of immunosuppressive drugs on cellular changes after antigenic stimulation and specialized cell function in the lymphoid and reticuloendothelial cell series. Topics include effects of immunosuppressive drugs on the sensitization process; cellular changes in lymphoid tissue following sensitization; and demonstration of differences in antigen handling among cells of the reticuloendothelial system. The text also takes a look at allogeneic inhibition and its possible relation to cell-bound immunity in vitro and the effects of immunosuppressive drugs at various stages of differentiation of immunologically competent cells. The publication examines a study of antibody-containing cells in the course of immunization and cellular differentiation during immune responses studied with electron microscope and radioautography. The text also elaborates on ambiguity in the translation of genetic code into proteins, induced by aminoglycoside antibiotics and immunosuppressive agents and cellular kinetics of immune response. The selection is a dependable source of information for readers interested in effects of drugs on antibody response and transplantation immunity.

Numerous developments in molecular biology have led to an explosive growth in the knowledge underlying mechanisms of carcinogenesis, cell signalling, tumor progression and development of metastasis. However, cure of cancer is still hampered by the inherited capacity of tumors to become resistant to standard therapies, to metastasize from their initial location and to proliferate in other tissue compartments. Radiotherapy is one of the main treatment modalities to achieve locoregional tumor control. However, the treatment of distant metastases further remains to be a challenge. In this special topic we are interested to elucidate immunological aspects which are initiated and affected by radiotherapy. We also aim to describe the development of innovative immunological strategies from a preclinical stage to clinical application which could be combined with standard radiotherapeutic approaches. A special interest will also deal with the effects of radiotherapy on tumor initiating cells as well as on the tumor microenvironment. Last but not least the effects of different irradiation sources and qualities such as photones, protones and heavy ions will be analyzed with respect to immunological outcome.

Cancer care is undergoing a radical transformation as novel technologies are directed toward new treatments and personalized medicine. The most dramatic advances in the treatment of cancer have come from therapeutics that augment the immune response to tumors. The immune checkpoint inhibitors are the best-known and most highly advanced examples of Immune Therapeutics targeting tumor cells and include approved antibody drugs directed at the cell surface proteins CTLA4 and PD-1. These are now considered foundational treatments for several solid tumor indications, and that list of indications is growing quickly. More broadly, antibodies have become workhorse molecules across the entire immunotherapy landscape. Antibodies to novel targets modulate the activity of diverse immune cell regulatory proteins. Engineered antibodies can induce tumor cell death or expose tumor cells to poisonous toxins (ADCC and ADC, respectively). Bi-specific antibodies can engage multiple tumor targets simultaneously, or can redirect lymphocytes to attack tumor cells. The antigen-binding domains within antibodies can be spliced onto cell stimulatory domains and transduced into T cells or NK cells, creating remarkable tumor-specific cellular therapeutics (CAR-T, CAR-NK). Beyond antibody-based therapies there are highly diverse and differentiated technology tool kits being applied to immunotherapy. Small molecule drugs are being developed to attack the tumor microenvironment, novel tumor vaccine approaches are showing great promise, patient lymphocytes are being isolated, expanded and reintroduced to patients, gene-editing techniques are becoming widely deployed, and a vast number of new tumor targets, and mutated tumor proteins (neoantigens), are being discovered. The past decade has seen unprecedented success in the treatment of diverse cancers. The authors of this volume have been asked to not only review progress to date, but importantly, to look ahead, and anticipate the evolution of cancer treatment across diverse Immune Therapeutic approaches. Our hypothesis is that the advances we are seeing across the immunotherapy landscape will further evolve and synergize, leading us finally to outright cures for many cancers.

Classically, anti-cancer therapies have always been applied with the primary aim of tumor debulking achieved through widespread induction of cancer cell death. While the role of host immune system is frequently considered as host protective in various (antigen-bearing) pathologies or infections yet in case of cancer overtime it was proposed that the host immune system either plays no role in therapeutic efficacy or plays a limited role that is therapeutically unemployable. The concept that the immune system is dispensable for the efficacy of anticancer therapies lingered on for a substantial amount of time; not only because evidence supporting the claim that anti-cancer immunity played a role were mainly contradictory, but also largely because it was considered acceptable (and sometimes still is) to test anticancer therapies in immunodeficient mice (i.e. SCID/athymic mice lacking adaptive immune system). This latter practice played a detrimental role in appreciating the role of anticancer immunity in cancer therapy. This scenario is epitomized by the fact that for a long time the very existence of cancer-associated antigens or cancer-associated ‘danger signaling’ remained controversial. However, over last several years this dogmatic view has been considerably modified. The existence of cancer-associated antigens and ‘danger signaling’ has been proven to be incontrovertible. These developments have together paved way for the establishment of the attractive concept of “immunogenic cell death” (ICD). It has been established that a restricted class of chemotherapeutics/targeted therapeutics, radiotherapy, photodynamic therapy and certain oncolytic viruses can induce a form of cancer cell death called ICD which is accompanied by spatiotemporally defined emission of danger signals. These danger signals along with other factors help cancer cells undergoing ICD to activate host innate immune cells, which in turn activate T cell-based immunity that helps eradicate live (or residual) surviving cancer cells. The emergence of ICD has been marred by some controversy. ICD has been criticized to be either experimental model or setting-specific or mostly a concept based on rodent studies that may have very limited implications for clinical application. However, in recent times it has emerged (through mainly retrospective or prognostic studies) that ICD can work in various human clinical settings hinting towards clinical applicability of ICD. However a widespread consensus on this issue is still transitional. In the current Research Topic we aimed to organize and intensify a discussion that strives to bring together the academic and clinical research community in order to provide a background to the current state-of-the-art in ICD associated bench-side research and to initiate fruitful discussions on present and future prospects of ICD translating towards the clinical, bedside reality.