| Autor: |
Kouji Matsushima, Satoru Ito, Kazuhiro Kakimi, Francis H.W. Shand, Etsuko Toda, Yuya Terashima, Shigeyuki Shichino, Kosuke Hachiga, Takuya Nakajima, Krishant Chand, Haru Ogiwara, Yoshiro Ishiwata, Shoji Yokochi, Satoshi Ueha |
| Rok vydání: |
2023 |
| DOI: |
10.1158/2326-6066.c.6548827.v1 |
| Popis: |
Depletion of CD4+ cells in tumor-bearing mice has strong antitumor effects. However, the mechanisms underlying these effects and the therapeutic benefits of CD4+ cell depletion relative to other immunotherapies have not been fully evaluated. Here, we investigated the antitumor effects of an anti–CD4-depleting mAb as a monotherapy or in combination with immune checkpoint mAbs. In B16F10, Colon 26, or Lewis lung carcinoma subcutaneous tumor models, administration of the anti-CD4 mAb alone had strong antitumor effects that were superior to those elicited by CD25+ Treg depletion or other immune checkpoint mAbs, and which were completely reversed by CD8+ cell depletion. CD4+ cell depletion led to the proliferation of tumor-specific CD8+ T cells in the draining lymph node and increased infiltration of PD-1+CD8+ T cells into the tumor, with a shift toward type I immunity within the tumor. Combination treatment with the anti-CD4 mAb and immune checkpoint mAbs, particularly anti–PD-1 or anti–PD-L1 mAbs, synergistically suppressed tumor growth and greatly prolonged survival. To our knowledge, this work represents the first report of robust synergy between anti-CD4 and anti–PD-1 or anti–PD-L1 mAb therapies. Cancer Immunol Res; 3(6); 631–40. ©2015 AACR. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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