scholarly journals Radiation therapy and immunotherapy—a potential combination in cancer treatment

2018 ◽  
Vol 25 (5) ◽  
Author(s):  
N. Asna ◽  
A. Livoff ◽  
R. Batash ◽  
R. Debbi ◽  
P. Schaffer ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Immune Checkpoint ◽  
Tumour Microenvironment ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade ◽  
Abscopal Effect ◽  
Immune Stimulation ◽  
Significant Development ◽  
Molecular Effects ◽  
Review Current

BackgroundRadiation therapy (rt) is a longstanding treatment modality for cancer. In addition, immune checkpoint blockade has been a significant development in the field of immunotherapy, modifying key immunosuppressive pathways of cancer cells.MethodsThe aim of the present work was to review current concepts of rt and immunotherapy synergism, the abscopal effect, and the molecular effects of rt in the tumour microenvironment, its influence on immune stimulation, and potential clinical outcomes that might evolve from ongoing studies. We also discuss potential predictors of clinical response.ResultsUp-to-date literature concerning the mechanisms, interactions, and latest knowledge about rt and immunotherapy was reviewed and summarized, and is presented here.ConclusionsThe possibility of using hyperfractionated rt to combine an abscopal effect with the enhanced effect of immune treatment using checkpoint blockade is a very promising method for future tumour treatments.

scholarly journals Radiotherapy-Mediated Immunomodulation and Anti-Tumor Abscopal Effect Combining Immune Checkpoint Blockade

Cancers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 2762 ◽  
Author(s):  
Xinrui Zhao ◽  
Chunlin Shao
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Immune Checkpoint ◽  
Tumor Regression ◽  
Combined Therapy ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade ◽  
Abscopal Effect ◽  
Specific Circumstance

Radiotherapy (RT) is a conventional method for clinical treatment of local tumors, which can induce tumor-specific immune response and cause the shrinkage of primary tumor and distal metastases via mediating tumor infiltration of CD8+ T cells. Ionizing radiation (IR) induced tumor regression outside the radiation field is termed as abscopal effect. However, due to the mobilization of immunosuppressive signals by IR, the activated CD8+T cells are not sufficient to maintain a long-term positive feedback to make the tumors regress completely. Eventually, the “hot” tumors gradually turn to “cold”. With the advent of emerging immunotherapy, the combination of immune checkpoint blockade (ICB) and local RT has produced welcome changes in stubborn metastases, especially anti-PD-1/PD-L1 and anti-CTLA-4 which have been approved in clinical cancer treatment. However, the detailed mechanism of the abscopal effect induced by combined therapy is still unclear. Therefore, how to formulate a therapeutic schedule to maximize the efficacy should be took into consideration according to specific circumstance. This paper reviewed the recent research progresses in immunomodulatory effects of local radiotherapy on the tumor microenvironment, as well as the unique advantage for abscopal effect when combined with ICB, with a view to exploring the potential application value of radioimmunotherapy in clinic.

scholarly journals Radiation, Immune Checkpoint Blockade and the Abscopal Effect: A Critical Review on Timing, Dose and Fractionation

2018 ◽  
Vol 8 ◽  
Author(s):  
Zachary S. Buchwald ◽  
Jacob Wynne ◽  
Tahseen H. Nasti ◽  
Simeng Zhu ◽  
Waleed F. Mourad ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
Critical Review ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade ◽  
Abscopal Effect

scholarly journals Combined High-Dose LATTICE Radiation Therapy and Immune Checkpoint Blockade for Advanced Bulky Tumors: The Concept and a Case Report

2021 ◽  
Vol 10 ◽  
Author(s):  
Liuqing Jiang ◽  
Xiaobo Li ◽  
Jianping Zhang ◽  
Wenyao Li ◽  
Fangfen Dong ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Immune Checkpoint ◽  
Radiation Treatment ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade ◽  
High Rate ◽  
Tumor Control ◽  
High Dose ◽  
Large Tumor ◽  
Fractionated Radiotherapy

Although the combination of immune checkpoint blockades with high dose of radiation has indicated the potential of co-stimulatory effects, consistent clinical outcome has been yet to be demonstrated. Bulky tumors present challenges for radiation treatment to achieve high rate of tumor control due to large tumor sizes and normal tissue toxicities. As an alternative, spatially fractionated radiotherapy (SFRT) technique has been applied, in the forms of GRID or LATTICE radiation therapy (LRT), to safely treat bulky tumors. When used alone in a single or a few fractions, GRID or LRT can be best classified as palliative or tumor de-bulking treatments. Since only a small fraction of the tumor volume receive high dose in a SFRT treatment, even with the anticipated bystander effects, total tumor eradications are rare. Backed by the evidence of immune activation of high dose radiation, it is logical to postulate that the combination of High-Dose LATTICE radiation therapy (HDLRT) with immune checkpoint blockade would be effective and could subsequently lead to improved local tumor control without added toxicities, through augmenting the effects of radiation in-situ vaccine and T-cell priming. We herein present a case of non-small cell lung cancer (NSCLC) with multiple metastases. The patient received various types of palliative radiation treatments with combined chemotherapies and immunotherapies to multiple lesions. One of the metastatic lesions measuring 63.2 cc was treated with HDLRT combined with anti-PD1 immunotherapy. The metastatic mass regressed 77.84% over one month after the treatment, and had a complete local response (CR) five months after the treatment. No treatment-related side effects were observed during the follow-up exams. None of the other lesions receiving palliative treatments achieved CR. The dramatic differential outcome of this case lends support to the aforementioned postulate and prompts for further systemic clinical studies.

scholarly journals Combining Radiation Therapy with Immune Checkpoint Blockade for Central Nervous System Malignancies

2016 ◽  
Vol 6 ◽  
Author(s):  
Neil M. D’Souza ◽  
Penny Fang ◽  
Jennifer Logan ◽  
Jinzhong Yang ◽  
Wen Jiang ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Radiation Therapy ◽  
Immune Checkpoint ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade
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