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Current explanations for the origin of tumor-infiltrating lymphocytes are based on the interaction between cancer cells and the immune system. This model was proposed before it was recognized that tumors are frequently infected or colonized by microbial elements, suggesting the presence of bacteria-specific and virus-specific T cells within tumors. While several aspects of this microbial experience remain under investigation, their impact on the tumor microenvironment and antitumor immune response may be significant, as the pathogens may elicit the direct or indirect recruitment of tumor-infiltrating lymphocytes. This \u201cInfection Hypothesis\u201d regarding the origin of tumor-infiltrating lymphocytes complements the classical tumor immunoediting hypothesis, offers new avenues for a comprehensive understanding of the tumor ecosystem, and highlights the need for more nuanced cancer treatment approaches that account for the potential interconnected roles of lymphocytes and pathogens in the tumor milieu.<\/jats:p>","DOI":"10.1136\/jitc-2026-015822","type":"journal-article","created":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T15:30:22Z","timestamp":1784215822000},"page":"e015822","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Diverse origin and nature of tumor-infiltrating lymphocytes: the infection hypothesis"],"prefix":"10.1136","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1259-2133","authenticated-orcid":false,"given":"Candelaria","family":"Gomez-Manzano","sequence":"first","affiliation":[{"name":"Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong Ho","family":"Shin","sequence":"additional","affiliation":[{"name":"Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Alvarez-Breckenridge","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9704-7459","authenticated-orcid":false,"given":"Andrew G","family":"Gillard","sequence":"additional","affiliation":[{"name":"Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Golnaz","family":"Morad","sequence":"additional","affiliation":[{"name":"Department of Tumor Microenvironment and Metastasis, H. 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