PD-1 blockade therapy augments the antitumor effects of lymphodepletion and adoptive T cell transfer
| Autor: | Aya Ohtsubo, Miyuki Sato, Toshiyuki Koya, Masashi Arita, Satoshi Shoji, Satoshi Hokari, Satoshi Watanabe, Ko Sato, Nobumasa Aoki, Toshiya Fujisaki, Ryo Suzuki, Toshiaki Kikuchi, Kosuke Ichikawa, Miho Takahashi, Yuki Sekiya, Yuko Abe, Masachika Hayashi, Yasuyoshi Ohshima, Koichiro Nozaki, Rie Kondo, Yu Saida |
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| Rok vydání: | 2021 |
| Předmět: |
Cancer Research
Adoptive cell transfer T cell Programmed Cell Death 1 Receptor Immunology CD8-Positive T-Lymphocytes Immunotherapy Adoptive Mice Immune system Neoplasms Tumor Microenvironment medicine Animals Humans Immunology and Allergy Cytotoxic T cell Tumor microenvironment biology Chemistry Adoptive Transfer Immune checkpoint medicine.anatomical_structure Oncology biology.protein Cancer research Antibody CD8 |
| Zdroj: | Cancer Immunology, Immunotherapy. 71:1357-1369 |
| ISSN: | 1432-0851 0340-7004 |
| Popis: | Lymphodepleting cytotoxic regimens enhance the antitumor effects of adoptively transferred effector and naive T cells. Although the mechanisms of antitumor immunity augmentation by lymphodepletion have been intensively investigated, the effects of lymphodepletion followed by T cell transfer on immune checkpoints in the tumor microenvironment remain unclear. The current study demonstrated that the expression of immune checkpoint molecules on transferred donor CD4+ and CD8+ T cells was significantly decreased in lymphodepleted tumor-bearing mice. In contrast, lymphodepletion did not reduce immune checkpoint molecule levels on recipient CD4+ and CD8+ T cells. Administration of anti-PD-1 antibodies after lymphodepletion and adoptive transfer of T cells significantly inhibited tumor progression. Further analysis revealed that transfer of both donor CD4+ and CD8+ T cells was responsible for the antitumor effects of a combination therapy consisting of lymphodepletion, T cell transfer and anti-PD-1 treatment. Our findings indicate that a possible mechanism underlying the antitumor effects of lymphodepletion followed by T cell transfer is the prevention of donor T cell exhaustion and dysfunction. PD-1 blockade may reinvigorate exhausted recipient T cells and augment the antitumor effects of lymphodepletion and adoptive T cell transfer. |
| Databáze: | OpenAIRE |
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