Cancer growth and progression are associated with immune suppression. Cancer cells have the ability to activate different immune checkpoint pathways that harbor immunosuppressive functions. Monoclonal antibodies that target immune checkpoints provided an immense breakthrough in cancer therapeutics. Among the immune checkpoint inhibitors, PD-1/PD-L1 and CTLA-4 inhibitors showed promising therapeutic outcomes, and some have been approved for certain cancer treatments, while others are under clinical trials. Recent reports have shown that patients with various malignancies benefit from immune checkpoint inhibitor treatment. However, mainstream initiation of immune checkpoint therapy to treat cancers is obstructed by the low response rate and immune-related adverse events in some cancer patients. This has given rise to the need for developing sets of biomarkers that predict the response to immune checkpoint blockade and immune-related adverse events. In this review, we discuss different predictive biomarkers for anti-PD-1/PD-L1 and anti-CTLA-4 inhibitors, including immune cells, PD-L1 overexpression, neoantigens, and genetic and epigenetic signatures. Potential approaches for further developing highly reliable predictive biomarkers should facilitate patient selection for and decision-making related to immune checkpoint inhibitor-based therapies.

Coronavirus disease 2019 (COVID‐19) is caused by SARS‐CoV‐2, a novel coronavirus strain. Some studies suggest that COVID‐19 could be an immune‐related disease, and failure of effective immune responses in initial stages of viral infection could contribute to systemic inflammation and tissue damage, leading to worse disease outcomes. T cells can act as a double‐edge sword with both pro‐ and anti‐roles in the progression of COVID‐19. Thus, better understanding of their roles in immune responses to SARS‐CoV‐2 infection is crucial. T cells primarily react to the spike protein on the coronavirus to initiate antiviral immunity; however, T‐cell responses can be suboptimal, impaired or excessive in severe COVID‐19 patients. This review focuses on the multifaceted roles of T cells in COVID‐19 pathogenesis and rationalizes their significance in eliciting appropriate antiviral immune responses in COVID‐19 patients and unexposed individuals. In addition, we summarize the potential therapeutic approaches related to T cells to treat COVID‐19 patients. These include adoptive T‐cell therapies, vaccines activating T‐cell responses, recombinant cytokines, Th1 activators and Th17 blockers, and potential utilization of immune checkpoint inhibitors alone or in combination with anti‐inflammatory drugs to improve antiviral T‐cell responses against SARS‐CoV‐2.

Regulatory T cells (Tregs) play essential roles in immune homeostasis; however, their role in tumor microenvironment (TME) is not completely evident. Several studies reported that infiltration of Tregs into various tumor tissues promotes tumor progression by limiting antitumor immunity and supporting tumor immune evasion. Furthermore, in TME, Tregs include heterogeneous subsets of cells expressing different immunosuppressive molecules favoring tumor progression. For an effective cancer therapy, it is critical to understand the Treg heterogeneity and biology in the TME. Recent studies have shown that immune checkpoint molecules promote cancer progression through various antitumor inhibitory mechanisms. Recent advances in cancer immunotherapy have shown the promising potentials of immune checkpoint inhibitors (ICIs) in inducing antitumor immune responses and clinical benefits in patients with cancer at late stages. Most studies revealed the effect of ICIs on T effector cells, and little is known about their effect on Tregs. In this review, we highlight the effects of the ICIs, including anti-CTLA-4, anti-PD-1/PD-L1, anti-LAG-3, anti-TIM-3, and anti-TIGIT, on tumor-infiltrating and peripheral Tregs to elicit effector T-cell functions against tumors. Additionally, we discuss how ICIs may target Tregs for cancer immunotherapy.