Tumor microenvironment, immune response and post-radiotherapy tumor clearance
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REVIEW ARTICLE
Tumor microenvironment, immune response and post‑radiotherapy tumor clearance M. I. Koukourakis1 · A. Giatromanolaki2 Received: 27 March 2020 / Accepted: 7 May 2020 © Federación de Sociedades Españolas de Oncología (FESEO) 2020
Abstract Radiotherapy is the treatment of choice for many cancer patients. Residual tumor leads to local recurrence after a period of an equilibrium created between proliferating, quiescent and dying cancer cells. The tumor microenvironment is a main obstacle for the efficacy of radiotherapy, as impaired blood flow leads to hypoxia, acidity and reduced accessibility of radiosensitizers. Eradication of remnant disease is an intractable clinical quest. After more than a century of research, anti-tumor immunity has gained a dominant position in oncology research and therapy. Immune cells play a significant role in the eradication of tumors during and after the completion of radiotherapy. The tumor equilibrium reached in the irradiated tumor may shift towards cancer cell eradication if the immune response is appropriately modulated. In the modern immunotherapy era, clinical trials are urged to standardize immunotherapy schemes that could be safely applied to improve clearance of the post-radiotherapy remnant disease. Keywords Radiotherapy · Immunotherapy · Residual disease · Tumor microenvironment
Introduction The history of cancer therapy with ionizing radiation goes back to 1896 when, just two years after the discovery of X-rays, Emil Grube treated a woman with recurrent breast carcinoma with X-rays [1]. During the following 120 years, important developments in tumor and normal tissue radiobiology, clinical trials, and technological advances established radiotherapy as a principal treatment modality, directly challenging the position of surgery in many diseases, like prostate cancer [2]. The curability of early stages of skin, prostate, bladder, cervical, head-neck, or even lung cancer, offered by radiotherapy exceeds 70%. In locally advanced stages, however, the results are far lower, the curability dropping below 40% depending upon the disease. Moreover, there are certainly highly radio-resistant types of tumors, like glioblastomas, hepatobiliary, and pancreatic carcinomas, or
* M. I. Koukourakis [email protected] 1
Department of Radiotherapy/Oncology, Democritus University of Thrace, 68100 Alexandroupolis, Greece
Department of Pathology, Democritus University of Thrace, 68100 Alexandroupolis, Greece
2
even locally advanced lung carcinomas, where curability is rather exceptional. The mechanisms of radiotherapy-induced cell death have been extensively explored, but there are certainly lots of biological aspects that remain obscure. The DNA has been considered as the main target of radiation damage, as single and double DNA strand breaks induced by free radicals produced by X-rays, or even directly induced by particle irradiation, lead to apoptosis or mitotic catastrophe [3]. More recently, the damage induced by radiation on cytoplasmic organelles and their
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