Lucas C M Arruda, Julia Karbach, Dragan Kiselicki, Hans-Michael Altmannsberger, Evgueni Sinelnikov, Dirk Gustavus, Hans Hoffmeister, Akin Atmaca, Elke Jäger
{"title":"肿瘤浸润性淋巴细胞衍生的CD8+克隆型浸润肿瘤组织并介导胶质母细胞瘤的肿瘤消退。","authors":"Lucas C M Arruda, Julia Karbach, Dragan Kiselicki, Hans-Michael Altmannsberger, Evgueni Sinelnikov, Dirk Gustavus, Hans Hoffmeister, Akin Atmaca, Elke Jäger","doi":"10.1080/2162402X.2025.2559784","DOIUrl":null,"url":null,"abstract":"<p><p>Adoptive cell therapy with tumor-infiltrating lymphocytes (TILs) has demonstrated consistent clinical efficacy in treating advanced melanoma and other \"hot\" tumors. However, it has shown limited success in \"cold\" tumors like glioblastoma. We present the successful treatment of a rapidly progressing glioblastoma patient with TILs expanded using a defined cytokine combination of IL-2, IL-15, and IL-21. The patient received lymphodepletion with cyclophosphamide one day pre-TIL infusion, followed by a single dose of IL-2 post-transfer. Complete tumor regression was observed after two TIL infusions administered two weeks apart. The TIL products were enriched for CD8<sup>+</sup> T-cells and demonstrated specific lysis of the autologous tumor cell line. Transcriptomic analysis of tumor biopsies post-TIL infusion revealed increased expression of genes associated with immunological synapse formation and T-cell effector function, correlating with the patient's clinical outcome. T-cell receptor (TCR) next-generation sequencing of the infused TILs and post-treatment tumor biopsies confirmed the infiltration and expansion of TIL-derived clonotypes within the tumor microenvironment. CD8<sup>+</sup> T-cell clonotypes exhibited robust tumor migration and expansion, while CD4<sup>+</sup> T-cells showed limited tumor infiltration. In conclusion, TILs expanded with IL-2/IL-15/IL-21 represent a promising therapeutic approach for glioblastoma, overcoming traditional challenges posed by the tumor microenvironment and achieving significant clinical outcomes.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"14 1","pages":"2559784"},"PeriodicalIF":6.5000,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Tumor-infiltrating lymphocytes-derived CD8<sup>+</sup> clonotypes infiltrate the tumor tissue and mediate tumor regression in glioblastoma.\",\"authors\":\"Lucas C M Arruda, Julia Karbach, Dragan Kiselicki, Hans-Michael Altmannsberger, Evgueni Sinelnikov, Dirk Gustavus, Hans Hoffmeister, Akin Atmaca, Elke Jäger\",\"doi\":\"10.1080/2162402X.2025.2559784\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Adoptive cell therapy with tumor-infiltrating lymphocytes (TILs) has demonstrated consistent clinical efficacy in treating advanced melanoma and other \\\"hot\\\" tumors. However, it has shown limited success in \\\"cold\\\" tumors like glioblastoma. We present the successful treatment of a rapidly progressing glioblastoma patient with TILs expanded using a defined cytokine combination of IL-2, IL-15, and IL-21. The patient received lymphodepletion with cyclophosphamide one day pre-TIL infusion, followed by a single dose of IL-2 post-transfer. Complete tumor regression was observed after two TIL infusions administered two weeks apart. The TIL products were enriched for CD8<sup>+</sup> T-cells and demonstrated specific lysis of the autologous tumor cell line. Transcriptomic analysis of tumor biopsies post-TIL infusion revealed increased expression of genes associated with immunological synapse formation and T-cell effector function, correlating with the patient's clinical outcome. T-cell receptor (TCR) next-generation sequencing of the infused TILs and post-treatment tumor biopsies confirmed the infiltration and expansion of TIL-derived clonotypes within the tumor microenvironment. CD8<sup>+</sup> T-cell clonotypes exhibited robust tumor migration and expansion, while CD4<sup>+</sup> T-cells showed limited tumor infiltration. In conclusion, TILs expanded with IL-2/IL-15/IL-21 represent a promising therapeutic approach for glioblastoma, overcoming traditional challenges posed by the tumor microenvironment and achieving significant clinical outcomes.</p>\",\"PeriodicalId\":48714,\"journal\":{\"name\":\"Oncoimmunology\",\"volume\":\"14 1\",\"pages\":\"2559784\"},\"PeriodicalIF\":6.5000,\"publicationDate\":\"2025-12-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Oncoimmunology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1080/2162402X.2025.2559784\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/10/7 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"IMMUNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Oncoimmunology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/2162402X.2025.2559784","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/10/7 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
Tumor-infiltrating lymphocytes-derived CD8+ clonotypes infiltrate the tumor tissue and mediate tumor regression in glioblastoma.
Adoptive cell therapy with tumor-infiltrating lymphocytes (TILs) has demonstrated consistent clinical efficacy in treating advanced melanoma and other "hot" tumors. However, it has shown limited success in "cold" tumors like glioblastoma. We present the successful treatment of a rapidly progressing glioblastoma patient with TILs expanded using a defined cytokine combination of IL-2, IL-15, and IL-21. The patient received lymphodepletion with cyclophosphamide one day pre-TIL infusion, followed by a single dose of IL-2 post-transfer. Complete tumor regression was observed after two TIL infusions administered two weeks apart. The TIL products were enriched for CD8+ T-cells and demonstrated specific lysis of the autologous tumor cell line. Transcriptomic analysis of tumor biopsies post-TIL infusion revealed increased expression of genes associated with immunological synapse formation and T-cell effector function, correlating with the patient's clinical outcome. T-cell receptor (TCR) next-generation sequencing of the infused TILs and post-treatment tumor biopsies confirmed the infiltration and expansion of TIL-derived clonotypes within the tumor microenvironment. CD8+ T-cell clonotypes exhibited robust tumor migration and expansion, while CD4+ T-cells showed limited tumor infiltration. In conclusion, TILs expanded with IL-2/IL-15/IL-21 represent a promising therapeutic approach for glioblastoma, overcoming traditional challenges posed by the tumor microenvironment and achieving significant clinical outcomes.
期刊介绍:
OncoImmunology is a dynamic, high-profile, open access journal that comprehensively covers tumor immunology and immunotherapy.
As cancer immunotherapy advances, OncoImmunology is committed to publishing top-tier research encompassing all facets of basic and applied tumor immunology.
The journal covers a wide range of topics, including:
-Basic and translational studies in immunology of both solid and hematological malignancies
-Inflammation, innate and acquired immune responses against cancer
-Mechanisms of cancer immunoediting and immune evasion
-Modern immunotherapies, including immunomodulators, immune checkpoint inhibitors, T-cell, NK-cell, and macrophage engagers, and CAR T cells
-Immunological effects of conventional anticancer therapies.