연구성과 홍보

Cell Rep Med. 2024 May 21;5(5):101567.

Title : IL-7-primed bystander CD8 tumor-infiltrating lymphocytes optimize the antitumor efficacy of T cell engager immunotherapy

Authors : Kun-Joo Lee1, Donghoon Choi2, Nara Tae3, Ha Won Song4, Yeon-Woo Kang1, Minji Lee2, Dain Moon1, Youngsik Oh1, Sujeong Park1, Ji-Hae Kim1, Siheon Jeong1, Jaehyuk Yang1, Uni Park1, Da Hee Hong5, Mi-Sun Byun5, Su-Hyung Park6, Joohyuk Sohn7, Yunji Park1, Sun-Kyoung Im2, Sun Shim Choi8*, Dae Hee Kim9*, Seung-Woo Lee10*

Affiliations :

1Department of Life Sciences, Pohang University of Science and Technology, Pohang 37673, Republic of Korea.

2Research Institute of NeoImmuneTech, Inc., Pohang 37673, Republic of Korea.

3Kangwon Institute of Inclusive Technology, Kangwon National University, Chuncheon 24341, Republic of Korea.

4Division of Biomedical Convergence, College of Biomedical Science, Institute of Bioscience & Biotechnology, Kangwon National University, Chuncheon 24341, Republic of Korea.

5Genexine Inc., Seoul 07789, Republic of Korea.

6Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon 34141, Republic of Korea.

7Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul 03722, Republic of Korea.

8Division of Biomedical Convergence, College of Biomedical Science, Institute of Bioscience & Biotechnology, Kangwon National University, Chuncheon 24341, Republic of Korea. 

9Kangwon Institute of Inclusive Technology, Kangwon National University, Chuncheon 24341, Republic of Korea; College of Pharmacy, Kangwon National University, Chuncheon 24341, Republic of Korea. 

10Department of Life Sciences, Pohang University of Science and Technology, Pohang 37673, Republic of Korea. 

DOI: 10.1016/j.xcrm.2024.101567.

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.