Radiation and immunotherapy: a synergistic combination

Abstract

Immunotherapy can be an effective treatment for metastatic cancer, but a significant subpopulation will not respond, likely due to the lack of antigenic mutations or the immune-evasive properties of cancer. Likewise, radiation therapy (RT) is an established cancer treatment, but local failures still occur. Clinical observations suggest that RT may expand the therapeutic reach of immunotherapy. We examine the immunobiologic and clinical rationale for combining RT and immunotherapy, two modalities yet to be used in combination in routine practice. Preclinical data indicate that RT can potentiate the systemic efficacy of immunotherapy, while activation of the innate and adaptive immune system can enhance the local efficacy of RT. IntroductionOver the past two decades, scientific and technological advances in immunotherapy have contributed to its role as one of the more promising cancer treatments. Previously, immunotherapy had been limited to nonspecific agents such as the Bacillus Calmette-Guerin vaccine, IL-2, and interferon-γ, but the characterization of cancer-specific antigens allowed for the emergence of cancer vaccines and cell-based therapies. In addition, immunobiologists identified checkpoints in immune regulation that led to the development of molecularly targeted approaches in cancer immunotherapy.Although immunotherapy is enticing because of occasional profound responses, it presently benefits a minority of patients in limited disease sites, and responses can be short lived. New combination approaches are needed to increase the efficacy of immunotherapy and expand its reach to other malignancies. Herein we describe the shortcomings of each immunotherapeutic modality. We then describe how radiation therapy (RT) counters immune evasion and how immunotherapy may potentiate local effects of RT. We also address the logistical aspects of combining RT with immunotherapy and discuss ongoing and future clinical applications.

Tumor cells PD-L1 expression as a favorable prognosis factor in nasopharyngeal carcinoma patients with pre-existing intratumor-infiltrating lymphocytes

“…Radiotherapy to induce immunogenic cell death to liberate neo-antigens has been used to induce T cell responses in combination with anti-PD-1. 42 Moreover, the survival curves of the present study were distinct and significantly different for the classification system based on intratumoral TILs and TCs-PD-L1 compared with those based on total TILs and TCs-PD-L1. Furthermore, this classification is a significant independent prognostic factor for OS and DFS in NPC patients.…”

An Abscopal Response to Radiation Therapy in a Patient with Metastatic Non-Small Cell Lung Cancer: A Case Report

“…The antitumor activity of cytotoxic T cells can be observed in the non-irradiated field. Such Abscopal responses can be achieved by irradiating either primary or metastatic tumors [13][14][15][16][17][18].…”

Cancer stem cell vaccine inhibits metastases of primary tumors and induces humoral immune responses against cancer stem cells

“…[1][2][3][4][5][6] Cancer stem cells (CSCs) mediate tumor metastasis by virtue of their relative resistance to chemotherapy and radiation therapy and contribute to relapse following treatment. 7,8 The inability to target CSCs with current therapies may be a significant factor for treatment failures.…”