Supplemental Tables 1 - 2, Figures 1 - 9 from Robust Antitumor Effects of Combined Anti–CD4-Depleting Antibody and Anti–PD-1/PD-L1 Immune Checkpoint Antibody Treatment in Mice

Ueha, Satoshi; Yokochi, Shoji; Ishiwata, Yoshiro; Ogiwara, Haru; Chand, Krishant; Nakajima, Takuya; Hachiga, Kosuke; Shichino, Shigeyuki; Terashima, Yuya; Toda, Etsuko; Shand, Francis H.W.; Kakimi, Kazuhiro; Ito, Satoru; Matsushima, Kouji

doi:10.1158/2326-6066.22538611.v1

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Supplemental Tables 1 - 2, Figures 1 - 9 from Robust Antitumor Effects of Combined Anti–CD4-Depleting Antibody and Anti–PD-1/PD-L1 Immune Checkpoint Antibody Treatment in Mice

journal contribution

posted on 2023-04-03, 23:10 authored by Satoshi Ueha, Shoji Yokochi, Yoshiro Ishiwata, Haru Ogiwara, Krishant Chand, Takuya Nakajima, Kosuke Hachiga, Shigeyuki Shichino, Yuya Terashima, Etsuko Toda, Francis H.W. Shand, Kazuhiro Kakimi, Satoru Ito, Kouji Matsushima

Table S1. Antibodies for flow cytometry and immunohistostaining. Table S2. Primers and probes used in real-time PCR. Supplementary Figure S1. Generation of B16F10-ÃŽ?hLNGFR transfected cells. Supplementary Figure S2. Optimization of the timing and dose for the administration of anti-CD4 mAb monotherapy. Supplementary Figure S3. Anti-CD4 mAb treatment decreases numbers of CD4+ T cells and pDCs in the blood, lymph nodes, spleen and tumor. Supplementary Figure S4. Intravascular staining distinguishes the intravascular and parenchymal leukocyte fractions in tumor tissue. Supplementary Figure S5. Anti-CD4 mAb treatment enhances the killing activity of tumor-infiltrating CD8+ T cells. Supplementary Figure S6. Anti-CD4 mAb treatment systemically increases the number of CD8+ CD44hi PD-1+ T cells. Supplementary Figure S7. Anti-CD4 mAb treatment causes proliferation of tumor-specific CD8+ T cells. Supplementary Figure S8. Anti-CD4 mAb treatment enhances proliferation of tumor-specific CD8+ T cells in the dLN. Supplementary Figure S9. Anti-CD4 mAb treatment or combination treatment with anti-CD4 and anti-PD-1 or PD-L1 mAbs induces anti-tumor gene expression within the tumor.

History

ARTICLE ABSTRACT

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.