CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题：Challenges for immunotherapy for the treatment of platinum resistant ovarian cancer.
Challenges for immunotherapy for the treatment of platinum resistant ovarian cancer.
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铂耐药卵巢癌通常定义为完成含铂治疗后6个月内进展，是一种异质性疾病，预后差、生存期短（不足18个月）。它通常被视为“冷肿瘤”，其特点是免疫细胞浸润减少，尤其是CD8+ T细胞。抗PD-1/PD-L1单药治疗的缓解率较低，不超过8%。目前正在研究多种治疗策略，通过联合化疗、抗血管生成药物、DNA损伤治疗（PARP抑制剂、环磷酰胺和/或放疗）或其他免疫检查点抑制剂（如CTLA-4抑制剂）来提高抗PD-1/PD-L1治疗的缓解率。卵巢透明细胞癌是一种罕见组织学亚型，以原发性铂耐药为特点；近期免疫检查点阻断治疗显示出个别但令人鼓舞的应答。其他免疫治疗方法，如过继T细胞治疗、疫苗，以及靶向髓系免疫检查点（例如“别吃我”信号CD47），也正在研究中。每种方法都面临各自的挑战，本文将对此进行综述。与在研试验同步开展扎实的免疫基因组学研究，将有助于优化这种致命疾病的免疫治疗联合方案，并确定预测性生物标志物。
Platinum resistant ovarian cancer, usually defined as progression occurring within 6 months after completing platinum-based therapy, is a heterogeneous disease with poor prognosis and short survival (less than 18 months). It is typically considered as a "cold tumor", characterized by reduced infiltration by immune cells, particularly CD8 + T cells. Response rate to anti-PD1/PD-L1 monotherapy is low, not exceeding 8%. Multiple therapeutic strategies are currently investigated in order to increase response rates to anti-PD1/PD-L1 through adding chemotherapy, anti-angiogenic agents, DNA damage (PARP inhibitors, cyclophosphamide and/or radiotherapy) or other immune checkpoint inhibitors (CTLA-4, etc.)
. Ovarian clear cell carcinoma, a rare histotype characterized by primary platinum-resistance, recently showed anecdotal but promising response rates to immune checkpoint blockade. Other immunotherapeutic approaches such as adoptive T cell therapy, vaccines and targeting myeloid immune checkpoints like "don't eat me" signal CD47 are currently investigated.
Each approach faces distinct challenges that will be reviewed here. Robust immunogenomics studies conducted in parallel of the ongoing trials will help into refining optimal immunotherapy combination for this lethal disease and identify predictive biomarkers.
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