2020 Volume 32 Issue 4 Pages 144-152
Immunotherapy, especially targeting immune inhibitory checkpoint pathways, has recently attracted much attention as a promising strategy in the treatment of cancer, since the anti-tumor efficacy induced by specific inhibitors called “immune checkpoint inhibitors （ICIs）” has been demonstrated even in patients with advanced metastatic cancer. However, the clinical outcome is extremely limited to some patients, and adverse events such as serious autoimmunity and hyperprogression have emerged. Many studies have been conducted worldwide to identify the genomic, molecular, microenvironmental and immunological mechanisms underlying ICI resistance, and numerous clinical trials have been conducted globally using newly generated antibodies targeting other IC molecules such as LAG3 and TIGIT in combination with other agents. Despite the enthusiasm, however, there has been little practical progress in clinical settings. There are two possible reasons: one is evolutional transformation of both tumor cells and host environment through the interplay between them, and the other is a loss of immune functions caused by tumor progression and metastasis. Thus, we need to better understand both tumor cells and host immunity together in order to disrupt the vicious spiral that leads to treatment resistance. This review highlights the current advances in immunotherapy and oncoimmune determinants driving the deterioration of tumor immunity for developing precision immunotherapy.
