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IL-7-primed bystander CD8 tumor-infiltrating lymphocytes optimize the antitumor efficacy of T cell engager immunotherapy.
Lee, Kun-Joo; Choi, Donghoon; Tae, Nara; Song, Ha Won; Kang, Yeon-Woo; Lee, Minji; Moon, Dain; Oh, Youngsik; Park, Sujeong; Kim, Ji-Hae; Jeong, Siheon; Yang, Jaehyuk; Park, Uni; Hong, Da Hee; Byun, Mi-Sun; Park, Su-Hyung; Sohn, Joohyuk; Park, Yunji; Im, Sun-Kyoung; Choi, Sun Shim; Kim, Dae Hee; Lee, Seung-Woo.
Afiliación
  • Lee KJ; Department of Life Sciences, Pohang University of Science and Technology, Pohang 37673, Republic of Korea.
  • Choi D; Research Institute of NeoImmuneTech, Inc., Pohang 37673, Republic of Korea.
  • Tae N; Kangwon Institute of Inclusive Technology, Kangwon National University, Chuncheon 24341, Republic of Korea.
  • Song HW; Division of Biomedical Convergence, College of Biomedical Science, Institute of Bioscience & Biotechnology, Kangwon National University, Chuncheon 24341, Republic of Korea.
  • Kang YW; Department of Life Sciences, Pohang University of Science and Technology, Pohang 37673, Republic of Korea.
  • Lee M; Research Institute of NeoImmuneTech, Inc., Pohang 37673, Republic of Korea.
  • Moon D; Department of Life Sciences, Pohang University of Science and Technology, Pohang 37673, Republic of Korea.
  • Oh Y; Department of Life Sciences, Pohang University of Science and Technology, Pohang 37673, Republic of Korea.
  • Park S; Department of Life Sciences, Pohang University of Science and Technology, Pohang 37673, Republic of Korea.
  • Kim JH; Department of Life Sciences, Pohang University of Science and Technology, Pohang 37673, Republic of Korea.
  • Jeong S; Department of Life Sciences, Pohang University of Science and Technology, Pohang 37673, Republic of Korea.
  • Yang J; Department of Life Sciences, Pohang University of Science and Technology, Pohang 37673, Republic of Korea.
  • Park U; Department of Life Sciences, Pohang University of Science and Technology, Pohang 37673, Republic of Korea.
  • Hong DH; Genexine Inc., Seoul 07789, Republic of Korea.
  • Byun MS; Genexine Inc., Seoul 07789, Republic of Korea.
  • Park SH; Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon 34141, Republic of Korea.
  • Sohn J; Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul 03722, Republic of Korea.
  • Park Y; Department of Life Sciences, Pohang University of Science and Technology, Pohang 37673, Republic of Korea.
  • Im SK; Research Institute of NeoImmuneTech, Inc., Pohang 37673, Republic of Korea.
  • Choi SS; Division of Biomedical Convergence, College of Biomedical Science, Institute of Bioscience & Biotechnology, Kangwon National University, Chuncheon 24341, Republic of Korea. Electronic address: schoi@kangwon.ac.kr.
  • Kim DH; Kangwon Institute of Inclusive Technology, Kangwon National University, Chuncheon 24341, Republic of Korea; College of Pharmacy, Kangwon National University, Chuncheon 24341, Republic of Korea. Electronic address: kimdh@kangwon.ac.kr.
  • Lee SW; Department of Life Sciences, Pohang University of Science and Technology, Pohang 37673, Republic of Korea. Electronic address: sw_lee@postech.ac.kr.
Cell Rep Med ; 5(5): 101567, 2024 May 21.
Article en En | MEDLINE | ID: mdl-38744277
ABSTRACT
Bispecific T cell engagers (TCEs) show promising clinical efficacy in blood tumors, but their application to solid tumors remains challenging. Here, we show that Fc-fused IL-7 (rhIL-7-hyFc) changes the intratumoral CD8 T cell landscape, enhancing the efficacy of TCE immunotherapy. rhIL-7-hyFc induces a dramatic increase in CD8 tumor-infiltrating lymphocytes (TILs) in various solid tumors, but the majority of these cells are PD-1-negative tumor non-responsive bystander T cells. However, they are non-exhausted and central memory-phenotype CD8 T cells with high T cell receptor (TCR)-recall capacity that can be triggered by tumor antigen-specific TCEs to acquire tumoricidal activity. Single-cell transcriptome analysis reveals that rhIL-7-hyFc-induced bystander CD8 TILs transform into cycling transitional T cells by TCE redirection with decreased memory markers and increased cytotoxic molecules. Notably, TCE treatment has no major effect on tumor-reactive CD8 TILs. Our results suggest that rhIL-7-hyFc treatment promotes the antitumor efficacy of TCE immunotherapy by increasing TCE-sensitive bystander CD8 TILs in solid tumors.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Linfocitos Infiltrantes de Tumor / Interleucina-7 / Linfocitos T CD8-positivos / Inmunoterapia Límite: Animals / Humans Idioma: En Revista: Cell Rep Med Año: 2024 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
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XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Linfocitos Infiltrantes de Tumor / Interleucina-7 / Linfocitos T CD8-positivos / Inmunoterapia Límite: Animals / Humans Idioma: En Revista: Cell Rep Med Año: 2024 Tipo del documento: Article Pais de publicación: Estados Unidos