Seledtsov V I, Goncharov A G, Seledtsova G V
a lmmanuel Kant Baltic Federal University ; Kaliningrad , Russia.
Hum Vaccin Immunother. 2015;11(4):851-69. doi: 10.1080/21645515.2015.1009814.
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.
免疫系统发挥着肿瘤破坏和肿瘤保护两种功能。成熟的树突状细胞（DCs）、经典激活的巨噬细胞（M1）、粒细胞、B淋巴细胞、αβ和γδ T淋巴细胞、自然杀伤T（NKT）细胞以及自然杀伤（NK）细胞可能参与抗肿瘤免疫保护。相反，耐受性DCs、交替激活的巨噬细胞（M2）、髓源性抑制细胞（MDSCs）以及调节性T（Tregs）和B细胞（Bregs）能够抑制抗肿瘤免疫反应。抗癌疫苗接种是引发抗肿瘤免疫反应同时克服免疫抑制机制的一种有效策略。完整的肿瘤细胞或其衍生的裂解物作为癌症疫苗比单个肿瘤相关抗原（TAAs）更具前景，因为疫苗细胞能够引发针对多种TAAs的免疫反应。基于癌细胞的疫苗可以是自体的、同种异体的或异种的。异种疫苗的临床应用具有优势，因为它们在打破对TAAs预先存在的免疫耐受方面可能最为有效。为了增强免疫治疗效果，疫苗接种可以与针对不同免疫途径的其他方式联合使用。这些方式包括：1）基于细胞的疫苗的基因或化学修饰；2）通过激活树突状细胞将TAAs交叉呈递给T细胞；3）T细胞过继性治疗；4）用非特异性免疫调节剂、Toll样受体（TLR）激动剂、细胞因子、趋化因子或激素刺激细胞毒性炎症；5）使用抗体、小分子减少免疫抑制和/或刺激抗肿瘤效应细胞；6）各种细胞减灭方式。作者设想，联合免疫治疗策略将在不久的将来使临床疗效得到显著改善。
