Abstract
Simple SummaryDrug development and therapeutic approaches for treating cancer have shifted towards incorporating more multimodality approaches that harness the immune system. Despite innovative and notable advances in immunotherapy, challenges associated with variations in patient response rates and efficacies on select tumors minimize the overall effectiveness of these immunotherapy approaches. This review provides an overview of the current immunotherapy options available, followed by epigenetic immunomodulators that may enhance and transmogrify immunotherapy effectiveness. These approaches are positioned to harness trained immunity, improve immune response rates, and increase the efficacy of immunotherapies.Cancer immunotherapy harnesses the immune system by targeting tumor cells that express antigens recognized by immune system cells, thus leading to tumor rejection. These tumor-associated antigens include tumor-specific shared antigens, differentiation antigens, protein products of mutated genes and rearrangements unique to tumor cells, overexpressed tissue-specific antigens, and exogenous viral proteins. However, the development of effective therapeutic approaches has proven difficult, mainly because these tumor antigens are shielded, and cells primarily express self-derived antigens. Despite innovative and notable advances in immunotherapy, challenges associated with variable patient response rates and efficacy on select tumors minimize the overall effectiveness of immunotherapy. Variations observed in response rates to immunotherapy are due to multiple factors, including adaptative resistance, competency, and a diversity of individual immune systems, including cancer stem cells in the tumor microenvironment, composition of the gut microbiota, and broad limitations of current immunotherapeutic approaches. New approaches are positioned to improve the immune response and increase the efficacy of immunotherapies, highlighting the challenges that the current global COVID-19 pandemic places on the present state of immunotherapy.
Highlights
Cancer accounted for nearly 10 million deaths in 2020 [1]
Camelliti et al have recently reported that, in a fraction of nonresponder patients varying from 4 to 29% based on clinical reports, there was an unexpected increase in tumor growth after immune checkpoint inhibitor (ICI) administration [20]
Cancer stem cells (CSC) have been characterized as expressing high levels of anti-apoptotic proteins, such as B-cell lymphoma 2 (Bcl-2) and survivin, which protect them from apoptosis-inducing immune effector T and natural killer cells (NK) cells [133]
Summary
Cancer accounted for nearly 10 million deaths in 2020 [1]. Over the past few decades, a broad range of therapeutic options has been developed for solid and non-solid tumors, including surgical therapy, chemotherapy, radiotherapy, and targeted therapies. Cancer immunotherapy using antibodies that target immune checkpoints has delivered outstanding results This type of cancer therapy is based on the premise that tumor cells express antigens and harness and modulate the body’s immune system to generate an anti-tumor response [11,12,13]. The development of practical therapeutic approaches, including cancer vaccines, has not proven efficacious because these tumor antigens are generally weak immunogens and self-derived antigens Another significant problem, especially for immune checkpoint inhibitor (ICI) therapy, is the changing expression of targeted receptors/checkpoints. HPD is defined as the sudden acceleration of tumor growth kinetics above its baseline growth rate with inherently unstable tumor genomics affecting crucial mechanisms of cell growth [18]
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