Korbelik Mladen, Banáth Judith, Zhang Wei
British Columbia Cancer Agency, Vancouver, BC V5Z 4E6, Canada.
Cancers (Basel). 2016 Oct 15;8(10):94. doi: 10.3390/cancers8100094.
Myeloid regulatory cells (Mregs) are, together with regulatory T cells (Tregs), a dominant effector population responsible for restriction of the duration and strength of antitumor immune response. Photodynamic therapy (PDT) and cancer vaccines generated by PDT are modalities whose effectiveness in tumor destruction is closely dependent on the associated antitumor immune response. The present study investigated whether the immunodepletion of granulocytic Mregs in host mice by anti-GR1 antibody would improve the response of tumors to PDT or PDT vaccines in these animals. Anti-GR1 administration immediately after Temoporfin-PDT of mouse SCCVII tumors abrogated curative effect of PDT. The opposite effect, increasing PDT-mediated tumor cure-rates was attained by delaying anti-GR1 treatment to 1 h post PDT. With PDT vaccines, multiple anti-GR1 administrations (days 0, 4, and 8 post vaccination) improved the therapy response with SCCVII tumors. The results with PDT suggest that neutrophils (boosting antitumor effect of this therapy) that are engaged immediately after photodynamic light treatment are within one hour replaced with a different myeloid population, presumably Mregs that hampers the therapy-mediated antitumor effect. Anti-GR1 antibody, when used with optimal timing, can improve the efficacy of both PDT of tumors in situ and PDT-generated cancer vaccines.
髓系调节细胞（Mregs）与调节性T细胞（Tregs）一起，是负责限制抗肿瘤免疫反应的持续时间和强度的主要效应细胞群体。光动力疗法（PDT）以及由PDT产生的癌症疫苗，其在肿瘤破坏方面的有效性与相关的抗肿瘤免疫反应密切相关。本研究调查了通过抗GR1抗体对宿主小鼠中的粒细胞Mregs进行免疫清除是否会改善这些动物中肿瘤对PDT或PDT疫苗的反应。在小鼠SCCVII肿瘤进行替莫泊芬-PDT后立即给予抗GR1消除了PDT的治疗效果。通过将抗GR1治疗推迟到PDT后1小时，获得了相反的效果，即提高了PDT介导的肿瘤治愈率。对于PDT疫苗，多次给予抗GR1（接种疫苗后第0、4和8天）改善了对SCCVII肿瘤的治疗反应。PDT的结果表明，在光动力光疗后立即参与（增强该疗法的抗肿瘤作用）的中性粒细胞在一小时内被不同的髓系细胞群体所取代，推测是阻碍该疗法介导的抗肿瘤作用的Mregs。抗GR1抗体在最佳时机使用时，可以提高原位肿瘤PDT和PDT产生的癌症疫苗的疗效。
