The discovery of immune checkpoint inhibitors (ICIs) has been a significant breakthrough in the field of cancer immunotherapy. By blocking T-cell inhibitory signals and allowing the immune system to mount a response against cancer cells, ICIs have been used to treat patients with a variety of cancer types. Currently, the US FDA has approved three categories of checkpoint inhibitors: PD-1 inhibitors (Nivolumab, Pembrolizumab, and Cemiplimab), PD-L1 inhibitors (Atezolizumab, Avelumab and Durvalumab) and one CTLA-4 inhibitor (Ipilimumab). But despite the fact that ICIs have received success in specific cancer types, such as hematological (blood) cancers like leukemia and lymphoma, they have relatively low response rates in patients suffering from epithelial (solid) cancers, limiting their use. This paper discusses possible improvements to checkpoint inhibitor therapy, including current predictive factors for response as well as mechanisms and possible improvements to PD-1/PD-L1 and CTLA-4 inhibitors. Through an exploration of current challenges to ICI therapy, clinical trials, biomarkers like the tumor mutation burden and multivariate model, and combination therapies to improve efficacy, this review aims to provide insight into potential strategies to enhance ICIs to treat a broader spectrum of cancers, leading to a more inclusive and effective treatment. While combination therapies often demonstrate enhanced efficacy, further research must be conducted to optimize treatment specifics for each cancer type. Although this review focuses on the potential of PD-1/PD-L1 and CTLA-4 inhibitors, it overlooks other novel checkpoint targets, which could offer a more broad perspective.
Ananya Devkirti (Sat,) studied this question.