尽管先天炎症细胞因子在已形成的人类肿瘤中的作用尚不清楚，但先天炎症促进肿瘤发展。在这里，我们报告了 Ib 期试验的临床和转化结果，该试验测试人类胰腺癌中的 IL-1β 阻断是否会减轻骨髓免疫抑制并揭示抗肿瘤 T 细胞对 PD-1 阻断的反应。初治晚期胰腺导管腺癌患者 (n=10) 接受卡那奴单抗、高亲和力单克隆人抗白细胞介素 1β (IL-1β)、PD-1 阻断抗体斯巴达珠单抗和吉西他滨/n(ab) 的治疗）紫杉醇。通过流式细胞术对试验中患者与接受多药化疗的患者的配对外周血进行分析，结果显示，试验中患者的 HLA-DR CD38 活化 CD8 T 细胞适度增加，循环单核骨髓源性抑制细胞 (MDSC) 减少，但不在控件中。同样，我们使用患者血清在体外分化单核细胞 MDSC，结果表明，当使用试验中患者的治疗血清样本时，T 细胞增殖的功能性抑制会减少，但使用单独化疗患者的血清时则不会。通过单细胞转录分析或多重免疫荧光评估，我们在肿瘤内观察到抑制性骨髓细胞群或活化 T 细胞的变化很少，尽管 CD8 T 细胞的增加表明肿瘤免疫微环境的改善可能会通过更大规模的研究来揭示。总体而言，数据表明，暴露于 PD-1 和 IL-1β 阻断剂会诱导外周 CD8 T 细胞适度重新激活，并减少循环单核 MDSC；然而，这些变化并没有导致肿瘤微环境发生类似的一致变化。

Innate inflammation promotes tumor development, although the role of innate inflammatory cytokines in established human tumors is unclear. Here we report clinical and translational results from a phase Ib trial testing whether IL-1β blockade in human pancreatic cancer would alleviate myeloid immunosuppression and reveal antitumor T-cell responses to PD-1 blockade. Patients with treatment-naïve advanced pancreatic ductal adenocarcinoma (n=10) were treated with canakinumab, a high-affinity monoclonal human anti-interleukin-1β (IL-1β), the PD-1 blocking antibody spartalizumab, and gemcitabine/n(ab)paclitaxel. Analysis of paired peripheral blood from patients in the trial versus patients receiving multiagent chemotherapy showed a modest increase in HLA-DR+CD38+ activated CD8+ T cells and a decrease in circulating monocytic myeloid-derived suppressor cells (MDSCs) by flow cytometry for patients in the trial, but not in controls. Similarly, we used patient serum to differentiate monocytic MDSCs in vitro and showed that functional inhibition of T-cell proliferation was reduced when using on-treatment serum samples from patients in the trial but not when using serum from patients treated with chemotherapy alone. Within the tumor we observed few changes in suppressive myeloid-cell populations or activated T cells as assessed by single-cell transcriptional profiling or multiplex immunofluorescence, although increases in CD8+ T cells suggest that improvements in the tumor immune microenvironment might be revealed by a larger study. Overall, the data indicate that exposure to PD-1 and IL-1β blockade induced a modest reactivation of peripheral CD8+ T cells and decreased circulating monocytic MDSCs; however, these changes did not lead to similarly uniform alterations in the tumor microenvironment.