Immunotherapy Special Collection
Exploring optimal sequencing of radiation and immunotherapy combinationsThe purpose of this article is to assemble, review, and provide a synopsis of the historical and current literature regarding optimal sequencing of radiation (RT) and immunotherapy combination treatments.
Role of noninvasive molecular imaging in determining responseThe intersection of immunotherapy and radiation oncology is a rapidly evolving area of preclinical and clinical investigation. The strategy of combining radiation and immunotherapy to enhance local and systemic antitumor immune responses is intriguing yet largely unproven in the clinical setting because the mechanisms of synergy and the determinants of therapeutic response remain undefined. In recent years, several noninvasive molecular imaging approaches have emerged as a platform to interrogate the tumor immune microenvironment.
Toxicity of radiation and immunotherapy combinationsAlthough immunotherapy is a rapidly emerging modality for cancer care, there have been multiple reports of fatal toxicities. There have also been cases of treatment-related deaths with combined non-immunotherapeutic biologic compounds with radiation therapy. Thus, provision of summative information appraising the safety of combinatorial immunotherapy and radiation therapy (iRT) is imperative. Because this has not been well characterized, this review summarizes the available evidence to date.
Field size effects on the risk and severity of treatment-induced lymphopenia in patients undergoing radiation therapy for solid tumorsRadiation-induced lymphopenia (RIL) is the result of direct toxicity to circulating lymphocytes as they traverse the irradiated field, occurs in 40% to 70% of patients who undergo conventional external beam radiation therapy, and is associated with worse outcomes in multiple solid tumors. As immunotherapy strategies evolve, a better understanding of radiation's effects on the immune system is needed in order to develop rational methods of combining RT with immunotherapy.
The DNA damage response in immunotherapy and radiationDeficiencies in DNA damage repair (DDR) and response represent a common alteration in tumors, and exploitation of this feature using therapeutics has become more prominent.
Role of the immunosuppressive microenvironment in immunotherapyImmunotherapy is reshaping cancer treatment paradigms; however, response rates to immune therapies are low and depend on the host's pre-existing antitumor immunity. The tumor microenvironment is comprised of malignant cells, stroma, and extracellular molecules and can hinder immune control of tumors. Herein, we review how anti-tumor immune responses are formed and how tumors avoid immune destruction. We also outline potential therapeutic targets in the immunosuppressive tumor microenvironment to promote immune control of tumors.
Generating antitumor immunity by targeted radiation therapy: Role of dose and fractionationAccumulating evidence supports the role of radiation therapy in the induction of antitumor immunity. With recent advancements in stereotactic radiation therapy, there is increasing appreciation that, when combined with immune checkpoint blockade, the type of radiation dose and fractionation regimen selected may both influence local tumor control and also affect the generation of immune responses that are important for systemic control. Although a broad range of radiation dose and fractionation schema have been tested in both the preclinical and clinical settings, recent preclinical evidence suggests the existence of a dose per fraction threshold beyond which radiation becomes less effective in generating tumor immune responses.