Cancer Immunotherapy Harnessing Innate and Adaptive Immune Effector Cells and PD-1 Immune Checkpoint Inhibitors

Dear Colleagues,

The idea of harnessing a patient’s immune system to combat cancer originated in the nineteenth century. Wilhelm Busch and Friedrich Fehleisen first described the association between the spontaneous regression of tumors and the development of erysipelas, induced by Streptococcus pyogenes. Subsequently, William B. Coley treated sarcoma patients with cultured streptococci, observing the shrinkage in malignant tumors. This suggested, of course, that the immune system, stimulated by infections, might be responsible for tumor regression. Based on these initial observations on the possible link between infections and tumor rejection, many researchers began to explore the development of immunotherapy of cancer. Most of the attempts were, however, unsuccessful until recently, owing to the lack of reproducibility, coupled with the complexity of the immune system.

The development of immune checkpoint inhibitors—anti-cytotoxic T lymphocyte antigen 4 (CTLA-4) mAb, anti-programmed death-1 (PD-1) mAb and anti-PD-1 ligand 1 (PD-L1) mAb, and chimeric antigen-receptor (CAR)-T cells—suddenly revolutionized cancer treatments in 2010s. The immune checkpoint molecules are physiologically negative regulators of T-cell activation and maintain self-tolerance. The rationale of immune checkpoint therapy is to target the host immune system, in particular, T cells. However, this does not impact malignant tumors per se, as in conventional treatments like chemotherapy and radiotherapy.  CAR-T cells-based therapy is successful for the treatment of B lymphoma. While the introduction of the immune checkpoint inhibitors and CAR-T cells has opened a new era for cancer therapy, the efficacy of the techniques is not yet satisfactory. It is thus imperative to further develop novel cancer immunotherapies, including both PD-1 immune checkpoint combination therapy and the adaptive transfer of immune effector cells, such as genetically- or chemically-modified CAR-T cells, γδ T cells, and NK cells. In order to improve the efficacy of such novel cancer treatments, it is essential to delineate the precise mechanism underlying the effect of modified immune effector cells on tumor cells. Within this Special Issue of Cells, we will highlight the molecular mechanisms and future directions of PD-1 immune checkpoint inhibitor combination therapy and immune effector cells-based immunotherapies. To this end, we invite the submission of original articles and reviews in this exciting field of research.

Prof. Dr. Yoshimasa Tanaka
Guest Editor

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