Current Advances in T-cell-Based Cancer Immunotherapy

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 spontaneous regression of tumors and the development of erysipelas caused by Streptococcus pyogenes. Subsequently, William B. Coley treated patients with sarcoma with cultured streptococci and observed the shrinkage of malignant tumors, suggesting 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 explored the development of immunotherapy of cancer. Most of the attempts had been, however, unsuccessful until recently because of the lack of reproducibility and the complexity of the immune system. Whereas increasing evidence had accumulated that the immune system, especially T cells, could recognize neoantigens derived from tumors, only limited success was achieved in developing T cell-based cancer immunotherapy. In fact, dark clouds were looming over the development of cancer immunotherapy even in the early 2000s.

The development of immnune checkpoint inhibitors, such as 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, suddenly revolutionized cancer treatments in the early 2010s. The immune checkpoint molecules are physiologically negative regulators of T cell activation and maintain self-tolerance. The rationale of this therapy is to target the host immune system, in particular, T cells, but not malignant tumors per se as in conventional treatments like chemotherapy and radiotherapy. Whereas the introduction of the immune checkpoint inhibitors opened the new era of cancer therapy, their efficacy is not yet satisfactory. It is thus imperative to further develop T-cell-based immunotherapies, including adoptive transfer of cytotoxic αβ T cells, chimeric antigen receptor T cells, and γδ T cells. In order to improve the efficacy of such T-cell-based cancer treatments, it is essential to delineate the precise mechanism underlying the effect of cultured or genetically-engineered T cells on tumor cells. Within this Special Issue of Cells, we will highlight the molecular mechanisms and future directions of T-cell-based immunotherapies, and we would highly appreciate the submission of original articles, reviews, commentaries, short reports, or protocols in this exciting field of research. Clinical studies are excluded from this Special Issue of Cells.

Prof. Dr. Yoshimasa Tanaka
Prof. Dr. Craig T. Morita
Guest Editors

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• T-cell-based cancer immunotherapy
• γδ T cells
• CAR-T cells
• immune checkpoint inhibitors
• combination therapy