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. 2021 Aug 20;9(8):e002279. doi: 10.1136/jitc-2020-002279

Figure 6.

Figure 6

ZSTK474 but not anti-CD25 mAb in combination with anti-PD-1 mAb increases memory T cells in vivo, resulting in augmented durable antitumor effects. (A) Effects of ZSTK474 and anti-PD-1 mAb either alone or in combination on induction of MPECs, TCF7+ T cells and CD62L+ T cells in vivo. The frequencies of MPECs, TCF7+ T cells and CD62L+ T cells in NY-ESO-1-specific CD8+ T cells in spleens, DLNs and tumors 16 days after tumor inoculation. (B, C) Durable antitumor effects of anti-PD-1 mAb alone or the combination. Mice that completely eradicated the initial CMS5a-NY-ESO-1 tumors by treatment with anti-PD-1 mAb with or without ZSTK474 were re-challenged with CMS5a-NY-ESO-1 (right hind flank) and parental CMS5a (left hind flank) 70 days after the initial tumor inoculation. Individual tumor growth curves for rechallenged CMS5a-NY-ESO-1 and parental CMS5a (B) and survival curves of the re-challenged mice (C). (D, E) CD8+ memory T cell responses in spleens, DLNs and tumors after rechallenge with CMS5a-NY-ESO-1 and parental CMS5a in mice that completely eradicated the initial CMS5a-NY-ESO-1 tumors by treatment with anti-PD-1 mAb with/without ZSTK474 or anti-CD25 mAb. The frequencies of NY-ESO-1 (D) or internal tumor antigen in CMS5a (CMS5a-intAg) (E) specific CD8+ T cells in spleens, DLNs and tumors after 52 days from the primary tumor inoculation. (F) Effect of anti-CD25 mAb (250 µg/dose; day −1, 150 µg/dose; day 6) on Tregs, NY-ESO-1-specific CD8+ T cells and MPECs. The frequencies of Tregs in CD4+ T cells, NY-ESO-1-specific CD8+ T cells in CD8+ T cells and MPECs in NY-ESO-1-specific CD8+ T cells in spleens, DLNs and tumors 14 days after tumor inoculation. Data in (A, D–F) are means±SE. Data in (B, C) show pooled data from two independent experiments. Statistical analyses were performed by Dunnett’s test (A, D–F) and Log rank test (C). *P<0.05; **p<0.01; *** p<0.001. DLNs, draining lymph nodes; mAbs, monoclonal antibodies; MPECs, memory precursor effector cells; ns, not significant.