Medical Scientist Training Program, University of Illinois College of Medicine, Chicago, IL, USA; Department of Surgery, Division of Surgical Oncology, University of Illinois at Chicago, Chicago, IL, USA.
Cleveland Clinic Taussig Cancer Institute, Cleveland, OH, USA.
Pharmacol Ther. 2022 Aug;236:108111. doi: 10.1016/j.pharmthera.2022.108111. Epub 2022 Jan 10.
Immune checkpoint inhibitors (ICIs) have transformed the treatment paradigm for several malignancies. While the use of single-agent or combined ICIs has achieved acceptable disease control rates in a variety of solid tumors, such approaches have yet to show substantial therapeutic efficacy in select difficult-to-treat cancer types. Recently, select chemotherapy regimens are emerging as extensive modifiers of the tumor microenvironment, leading to the reprogramming of local immune responses. Accordingly, data is now emerging to suggest that certain anti-neoplastic agents modulate various immune cell processes, most notably the cross-presentation of tumor antigens, leukocyte trafficking, and cytokine biosynthesis. As such, the combination of ICIs and cytotoxic chemotherapy are beginning to show promise in many cancers that have long been considered poorly responsive to ICI-based immunotherapy. Here, we discuss past and present attempts to advance chemo-immunotherapy in these difficult-to-treat cancer histologies, mechanisms through which select chemotherapies modify tumor immunogenicity, as well as important considerations when designing such approaches to maximize efficacy and improve therapeutic response rates.
免疫检查点抑制剂 (ICIs) 已经改变了多种恶性肿瘤的治疗模式。虽然单药或联合使用 ICI 在多种实体瘤中已达到可接受的疾病控制率，但在某些治疗困难的癌症类型中，这些方法尚未显示出显著的治疗效果。最近，一些化疗方案被广泛认为是肿瘤微环境的调节剂，导致局部免疫反应的重新编程。因此，现在有数据表明，某些抗肿瘤药物调节各种免疫细胞过程，尤其是肿瘤抗原的交叉呈递、白细胞迁移和细胞因子生物合成。因此，ICI 和细胞毒性化疗的联合治疗开始在许多长期以来被认为对 ICI 为基础的免疫治疗反应不佳的癌症中显示出希望。在这里，我们讨论过去和现在在这些治疗困难的癌症组织学中推进化疗免疫治疗的尝试，以及选择化疗药物改变肿瘤免疫原性的机制，以及在设计这些方法以最大限度提高疗效和改善治疗反应率时需要考虑的重要因素。
