Abstract:
During the last decade, the dynamics of the cellular crosstalk have highlighted the significance of the host vs. tumor interaction. This resulted in the development of novel immunotherapeutic strategies in order to modulate/inhibit the mechanisms leading to escape of tumor cells from immune surveillance. Different monoclonal antibodies directed against immune checkpoints, e.g., the T lymphocyte antigen 4 and the programmed cell death protein 1/ programmed cell death ligand 1 have been successfully implemented for the treatment of cancer. Despite their broad activity in many solid and hematologic tumor types, only 20-40% of patients demonstrated a durable treatment response. This might be due to an impaired T cell tumor interaction mediated by immune escape mechanisms of tumor and immune cells as well as alterations in the composition of the tumor microenvironment, peripheral blood, and microbiome. These different factors dynamically regulate different steps of the cancer immune process thereby negatively interfering with the T cell -mediated anti-tumoral immune responses. Therefore, this review will summarize the current knowledge of the different players involved in inhibiting tumor immunogenicity and mounting resistance to checkpoint inhibitors with focus on the role of tumor T cell interaction. A better insight of this process might lead to the development of strategies to revert these inhibitory processes and represent the rational for the design of novel immunotherapies and combinations in order to improve their efficacy.
摘要:
在过去的十年里,细胞串扰的动力学突出了主机与肿瘤相互作用。这导致了新的免疫治疗策略的发展,以便调节/抑制导致肿瘤细胞从免疫监视中逃逸的机制。针对免疫检查点的不同单克隆抗体,例如,T淋巴细胞抗原4和程序性细胞死亡蛋白1/程序性细胞死亡配体1已成功用于癌症的治疗。尽管它们在许多实体和血液肿瘤类型中具有广泛的活性,只有20-40%的患者表现出持久的治疗反应.这可能是由于肿瘤和免疫细胞的免疫逃逸机制以及肿瘤微环境组成的改变介导的T细胞肿瘤相互作用受损。外周血,和微生物组。这些不同的因子动态地调节癌症免疫过程的不同步骤,从而负面地干扰T细胞介导的抗肿瘤免疫应答。因此,这篇综述将总结目前参与抑制肿瘤免疫原性和提高检查点抑制剂抗性的不同参与者的知识,重点是肿瘤T细胞相互作用的作用。对该过程的更好了解可能导致开发策略以恢复这些抑制过程,并代表设计新型免疫疗法和组合以提高其功效的合理性。