Myeloid immunosuppression and immune checkpoints in the tumor microenvironment

Tumor-promoting inflammation and the avoidance of immune destruction are hallmarks of cancer.While innate immune cells,such as neutrophils,monocytes,and macrophages,are critical mediators for sterile and nonsterile inflammation,persistent inflammation,such as that which occurs in cancer,is known to disturb normal myelopoiesis.This disturbance leads to the generation of immunosuppressive myeloid cells,such as myeloid-derived suppressor cells(MDSCs)and tumor-associated macrophages(TAMs).Due to their potent suppressive activities against effector lymphocytes and their abundance in the tumor microenvironment,immunosuppressive myeloid cells act as a major barrier to cancer immunotherapy.Indeed,various therapeutic approaches directed toward immunosuppressive myeloid cells are actively being tested in preclinical and clinical studies.These include antiinflammatory agents,therapeutic blockade of the mobilization and survival of myeloid cells,and immunostimulatory adjuvants.More recently,immune checkpoint molecules expressed on tumor-infiltrating myeloid cells have emerged as potential therapeutic targets to redirect these cells to eliminate tumor cells.In this review,we discuss the complex crosstalk between cancer-related inflammation and immunosuppressive myeloid cells and possible therapeutic strategies to harness antitumor immune responses.

Cancer Res:HDAC抑制剂可促进单抗药物对HER2阳性肿瘤的治疗效果

最近来自澳大利亚墨尔本的研究人员发现组蛋白去乙酰化酶抑制剂可以发动宿主免疫作为其抗肿瘤效应的一个基础。该研究为增强一些肿瘤免疫治疗药物的杀伤作用提供了新的方向。在这项发表在国际学术期刊Cancer Research上的研究中，研究人员发现组蛋白去乙酰化酶抑制剂panobinostat可以通过宿主免疫增强trastuzumab这种单抗治疗药物的抗肿瘤效果。