Rationale and evidence to combine radiation therapy and immunotherapy for cancer treatment

Abstract

Cancer immunotherapy exploits the immune system's ability to differentiate between tumor target cells and host cells. Except for limited success against a few tumor types, most immunotherapies have not achieved the desired clinical efficacy until recently. The field of cancer immunotherapy has flourished with a variety of new agents for clinical use, and remarkable progress has been made in the design of effective immunotherapeutic regimens. Furthermore, the therapeutic outcome of these novel agents is enhanced when combined with conventional cancer treatment modalities including radiotherapy (RT). An increasing number of studies have demonstrated the abscopal effect, an immunologic response occurring in cancer sites distant from irradiated areas. The present work reviews studies on the combination between RT and immunotherapy to induce synergistic and abscopal effects involved in cancer immunomodulation. Further insight into the complex interactions between the immune system and cancer cells in the tumor microenvironment, and their modulation by RT, may reveal the abscopal effect as a clinically relevant and reproducible event leading to improved cancer outcome.

Hunting for abscopal and bystander effects: clinical exploitation of non-targeted effects induced by partial high-single-dose irradiation of the hypoxic tumour segment in oligometastatic patients

“…Our knowledge on RIBEs derives mostly from preclinical studies. The RIAE and RIBE do however exist, as demonstrated here, and they can be intentionally induced by radiation, leading to partial and/or complete long lasting regression of metastatic disease [19]. It is still unclear why these non-targeted effects have only been seen sporadically until now.…”

Synergistic effects of anti-PDL-1 with ablative radiation comparing to other regimens with same biological effect dose based on different immunogenic response

“…Irradiation has multiple inhibitory and stimulatory effects on the immune system such as increased CD4 + , CD8 + and Treg Cells infiltration into TME [3,4] Some regimens of radiation like ablative RT was associated with increased infiltration of exhausted CD8+ T cells into the tumor, which induced radiation resistance. [5,6]. The combination of radiotherapy and Immune checkpoint blockers therapy can reduce these inhibitory effects by stimulating immune cells and enhancing the response to radiation.…”

Safety and efficacy of concurrent immune checkpoint inhibitors and hypofractionated body radiotherapy

“…Preclinical studies have shown that the combination of RT with ICIs is more effective than either treatment modality alone. [22][23][24][25][26][27] Despite the hype, such treatment combinations are still far from standard clinical practice, because the optimal timing, dosing, and fractionation of RT to yield the best synergistic outcomes remain uncertain. Moreover, data on the safety of such combinations are scarce.…”