免疫系统发挥肿瘤破坏性和肿瘤保护功能。成熟的树突状细胞(DC),经典激活的巨噬细胞(M1),粒细胞,B淋巴细胞,αβ和δT淋巴细胞,自然杀伤T(NKT)细胞,自然杀伤(NK)细胞可能参与抗肿瘤免疫保护。相反,致耐受性DCs,交替激活的巨噬细胞(M2),骨髓来源的抑制细胞(MDSCs),和调节性T(Tregs)和B细胞(Bregs)能够抑制抗肿瘤免疫应答。抗癌疫苗接种是引发抗肿瘤免疫反应的有用策略。同时克服免疫抑制机制。完整肿瘤细胞或其来源的裂解物比单个肿瘤相关抗原(TAA)更有希望作为癌症疫苗,因为疫苗细胞可以引发对多种TAA的免疫应答。基于癌细胞的疫苗可以是自体的,同种异体或异种。异种疫苗的临床应用是有利的,因为它们可以最有效地打破预先存在的对TAA的免疫耐受。为了加强免疫治疗,疫苗接种可以与针对不同免疫途径的其他方式相结合。这些方式包括1)基于细胞的疫苗的遗传或化学修饰;2)通过接合树突状细胞将TAA交叉引发T细胞;3)T细胞过继性治疗;4)通过非特异性免疫调节剂刺激细胞毒性炎症,toll样受体(TLR)激动剂,细胞因子,趋化因子或激素;5)使用抗体减少免疫抑制和/或刺激抗肿瘤效应细胞,小分子;和6)各种细胞还原模式。作者设想联合的免疫治疗策略将允许在不久的将来临床结果的实质性改善。
The immune system exerts both tumor-destructive and tumor-protective functions. Mature dendritic cells (DCs), classically activated macrophages (M1), granulocytes, B lymphocytes, aβ and ɣδ T lymphocytes, natural killer T (NKT) cells, and natural killer (NK) cells may be implicated in antitumor immunoprotection. Conversely, tolerogenic DCs, alternatively activated macrophages (M2), myeloid-derived suppressor cells (MDSCs), and regulatory T (Tregs) and B cells (Bregs) are capable of suppressing antitumor immune responses. Anti-cancer vaccination is a useful strategy to elicit antitumor immune responses, while overcoming immunosuppressive mechanisms. Whole tumor cells or lysates derived thereof hold more promise as cancer vaccines than individual tumor-associated antigens (TAAs), because vaccinal cells can elicit immune responses to multiple TAAs. Cancer cell-based vaccines can be autologous, allogeneic or xenogeneic. Clinical use of xenogeneic vaccines is advantageous in that they can be most effective in breaking the preexisting immune tolerance to TAAs. To potentiate immunotherapy, vaccinations can be combined with other modalities that target different immune pathways. These modalities include 1) genetic or chemical modification of cell-based vaccines; 2) cross-priming TAAs to T cells by engaging dendritic cells; 3) T-cell adoptive therapy; 4) stimulation of cytotoxic inflammation by non-specific immunomodulators, toll-like receptor (TLR) agonists, cytokines, chemokines or hormones; 5) reduction of immunosuppression and/or stimulation of antitumor effector cells using antibodies, small molecules; and 6) various cytoreductive modalities. The authors envisage that combined immunotherapeutic strategies will allow for substantial improvements in clinical outcomes in the near future.