Radiation therapy and immunotherapy: what is the optimal timing or sequencing?

• Published in: Immunotherapy Vol. 10; no. 4; pp. 299 - 316
• Main Authors: Aliru, Maureen L, Schoenhals, Jonathan E, Venkatesulu, Bhanu P, Anderson, Clark C, Barsoumian, Hampartsoum B, Younes, Ahmed I, K Mahadevan, Lakshmi S, Soeung, Melinda, Aziz, Kathryn E, Welsh, James W, Krishnan, Sunil
• Format: Journal Article
• Language: English
• Published: England Future Medicine Ltd 01.02.2018
• Subjects: adoptive cell therapy; Animals; Antigens; Apoptosis; Breast cancer; cancer immunotherapy; Cancer therapies; Cancer vaccines; Cell division; Clinical Protocols; combination therapy; CTLA4; Cytokines; Cytotoxicity; Deoxyribonucleic acid; Disease Models, Animal; DNA; DNA damage; DNA methylation; Humans; immune checkpoint inhibitors; Immune system; Immunological tolerance; Immunotherapy; Immunotherapy - methods; Ligands; Lymphocytes; Melanoma; Metastases; Metastasis; Mice; Molecular modelling; Neoplasms - immunology; Neoplasms - radiotherapy; Neoplasms - therapy; PD1/PDL1; Prostate cancer; radiation; Radiation therapy; Review; sequence; Signal transduction; timing; Tumor cells; Tumors; Vaccines; sequence; PD1/PDL1; cancer vaccines; radiation; timing; cancer immunotherapy; CTLA4; combination therapy; cytokines; immune checkpoint inhibitors; adoptive cell therapy
• ISSN: 1750-743X; 1750-7448
• DOI: 10.2217/imt-2017-0082

Radiotherapy is a component of the standard of care for many patients with locally advanced nonmetastatic tumors and increasingly those with oligometastatic tumors. Despite encouraging advances in local control and progression-free and overall survival outcomes, continued manifestation of tumor progression or recurrence leaves room for improvement in therapeutic efficacy. Novel combinations of radiation with immunotherapy have shown promise in improving outcomes and reducing recurrences by overcoming tumor immune tolerance and evasion mechanisms via boosting the immune system's ability to recognize and eradicate tumor cells. In this review, we discuss preclinical and early clinical evidence that radiotherapy and immunotherapy can improve treatment outcomes for locally advanced and metastatic tumors, elucidate underlying molecular mechanisms and address strategies to optimize timing and sequencing of combination therapy for maximal synergy.