{"doi":"10.3389/fimmu.2022.984318","title":"Pulsed radiotherapy to mitigate high tumor burden and generate immune memory","abstract":"Radiation therapy (XRT) has a well-established role in cancer treatment. Given the encouraging results on immunostimulatory effects, radiation has been increasingly used with immune-check-point inhibitors in metastatic disease, especially when immunotherapy fails due to tumor immune evasion. We hypothesized that using high-dose stereotactic radiation in cycles (pulses) would increase T-cell priming and repertoire with each pulse and build immune memory in an incremental manner. To prove this hypothesis, we studied the combination of anti-CTLA-4 and Pulsed radiation therapy in our 344SQ non-small cell lung adenocarcinoma murine model. Primary and secondary tumors were bilaterally implanted in 129Sv/Ev mice. In the Pulsed XRT group, both primary and secondary tumors received 12Gyx2 radiation one week apart, and blood was collected seven days afterwards for TCR repertoire analysis. As for the delayed-Pulse group, primary tumors received 12Gyx2, and after a window of two weeks, the secondary tumors received 12Gyx2. Blood was collected seven days after the second cycle of radiation. The immunotherapy backbone for both groups was anti-CTLA-4 antibody to help with priming. Treatment with Pulsed XRT + anti-CTLA-4 led to significantly improved survival and resulted in a delayed tumor growth, where we observed enhanced antitumor efficacy at primary tumor sites beyond XRT + anti-CTLA-4 treatment group. More importantly, Pulsed XRT treatment led to increased CD4 + effector memory compared to single-cycle XRT. Pulsed XRT demonstrated superior efficacy to XRT in driving antitumor effects that were largely dependent on CD4 + T cells and partially dependent on CD8 + T cells. These results suggest that combinatorial strategies targeting multiple points of tumor immune evasion may lead to a robust and sustained antitumor response.","journal":"Frontiers in Immunology","year":2022,"id":259127,"datarank":0.5812256558641298,"base_score":2.8903717578961645,"endowment":2.8903717578961645,"self_citation_contribution":0.4335557636844247,"citation_network_contribution":0.1476698921797051,"self_endowment_contribution":0.4335557636844247,"citer_contribution":0.1476698921797051,"corpus_percentile":null,"corpus_rank":null,"citation_count":17,"citer_count":8,"citers_with_citation_signal":5,"citers_with_endowment":5,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9625,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":244397,"name":"Hampartsoum B. Barsoumian","orcid":"0000-0002-8209-6119","position":1,"is_corresponding":false},{"id":267638,"name":"Kewen He","orcid":"0000-0003-0068-7191","position":2,"is_corresponding":false},{"id":268453,"name":"Yun Hu","orcid":"0000-0001-5597-9234","position":3,"is_corresponding":false},{"id":590501,"name":"Qi Wang","orcid":"0000-0002-1941-5287","position":4,"is_corresponding":false},{"id":724608,"name":"Chike O. Abana","orcid":"0000-0003-0209-8470","position":5,"is_corresponding":false},{"id":492723,"name":"Nahum Puebla‐Osorio","orcid":"0000-0001-6498-5230","position":6,"is_corresponding":false},{"id":725199,"name":"Ethan Hsu","orcid":null,"position":7,"is_corresponding":false},{"id":268454,"name":"Mark Wasley","orcid":"0000-0001-7243-7146","position":8,"is_corresponding":false},{"id":244402,"name":"Fatemeh Masrorpour","orcid":"0000-0001-5107-3275","position":9,"is_corresponding":false},{"id":399560,"name":"Jing Wang","orcid":"0000-0001-9413-2378","position":10,"is_corresponding":false},{"id":244406,"name":"María Angélica Cortez","orcid":"0000-0002-3130-4002","position":11,"is_corresponding":false},{"id":236007,"name":"James W. Welsh","orcid":"0000-0002-2255-8502","position":12,"is_corresponding":false},{"id":492721,"name":"Duygu Sezen","orcid":"0000-0002-4505-2280","position":0,"is_corresponding":true}],"reference_count":47,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T00:25:47.305414Z","pmid":"36275767","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}