Advances in Cancer Immunotherapy in Solid Tumors

Abstract

Immunotherapy is heralded as one of the most important advances in oncology. Until recently, only limited immunotherapeutic options were available in selected immunogenic cancers like melanoma and renal cell carcinomas. Nowadays, there is an improved understanding that anti-tumor immunity is controlled by a delicate balance in the tumor microenvironment between immune stimulatory and immune inhibitory pathways. Either by blocking the inhibitory pathways or stimulating the activating pathways that regulate cytotoxic lymphocytes, anti-tumor immunity can be enhanced leading to durable anti-tumor responses. Drugs which block the immune regulatory checkpoints namely the PD-1/PDL1 and CTLA 4 pathway have shown tremendous promise in a wide spectrum of solid and hematological malignancies, significantly improving overall survival in newly diagnosed and heavily pretreated patients alike. Hence there is renewed enthusiasm in the field of immune oncology with current research focused on augmenting responses to checkpoint inhibitors by combination therapy as well as studies looking at other immune modulators and adoptive T cell therapy. In this article, we highlight the key clinical advances and concepts in immunotherapy with particular emphasis on checkpoint inhibition as well as the future direction in this field.

A HER2-Targeting Antibody–Drug Conjugate, Trastuzumab Deruxtecan (DS-8201a), Enhances Antitumor Immunity in a Mouse Model

“…ICIs show remarkable antitumor effects in patients with various cancers (12)(13)(14). However, only a limited number of patients respond to ICIs (15).…”

“…Recently, immune checkpoint inhibitors (ICI) have been demonstrated to show remarkable clinical benefits (12)(13)(14). Nevertheless, there are many patients who are not sensitive or are refractory to a single agent of ICI, and combination therapies with other drugs are needed (15).…”

Enrichment and Characterization of the Tumor Immune and Non-immune Microenvironments in Established Subcutaneous Murine Tumors

“…, immune checkpoint inhibitors, chimeric antigen receptor T-cells, etc .) have the potential to induce durable cancer regressions; however, they remain relatively ineffective in solid tumor cancers 4,5 . Numerous groups have shown the critical hurdle that the TIME can play on treatment success 6,7 , and thus, there remains a need to accurately evaluate new immunotherapies in the pre-clinical setting specifically focusing on their ability to modulate or overcome the TIME 8 .…”

New horizons from immunotherapy in malignant pleural mesothelioma

“…Along this line, a number of immunotherapeutic clinical trials, aimed at activating the host's immune system or overcoming components of the immunosuppressive tumor microenvironment, have been activated (17). Among these, the two main approaches of immunotherapy currently under investigation in MPM are focused on the targeting of immune-checkpoint inhibitors and mesothelin.…”