Future of immune checkpoint inhibitors: focus on tumor immune microenvironment.

Immunotherapy has become a powerful clinical strategy in cancer treatment. Immune checkpoint inhibitors (ICIs) have opened a new era for cancer immunotherapy. Nowadays, the number of immunotherapy drug approvals has increased, with numerous treatment options in clinical and preclinical development. However, there remain some obstacles to improve the efficacy of ICIs further. The tumor immune microenvironment (TIME) consists of cancer cell, immune cells and cytokines, et cetera. The dynamics of TIME determine the efficacies of ICIs. Although the ICIs showed manageable toxicity, immune-related adverse effects (irAEs) are still unignorable for clinicians. Since some primary resistance mechanisms exist in TIME, ICIs can only show effects in individual cancer patients. Even for the patients who responded, acquired resistance will occur to neutralize the effect of ICIs. Understanding how to increase the response rates and overcome the resistance to various classes of ICIs is the key to improving clinical efficacy. Besides the novel ICIs in development, there are some approaches to establish combination therapies are underway to improve further the efficacies of ICIs in treating cancer patients. Here, we describe the complicated TIME and state quo of ICIs to prospect the future of ICIs in cancer treatment.