Bernson Elin, Huhn Oisín, Karlsson Veronika, Hawkes Delia, Lycke Maria, Cazzetta Valentina, Mikulak Joanna, Hall James, Piskorz Anna M, Portuesi Rosalba, Vitobello Domenico, Fiamengo Barbara, Siesto Gabriele, Horowitz Amir, Ghadially Hormas, Mavilio Domenico, Brenton James D, Sundfeldt Karin, Colucci Francesco
Department of Obstetrics and Gynaecology, University of Cambridge School of Clinical Medicine, NIHR Cambridge Biomedical Research Centre, Addenbrooke's Hosptial, Cambridge CB2 0QQ, UK.
Sahlgrenska Center for Cancer Research, Department of Obstetrics and Gynecology, Institute of Clinical Sciences, University of Gothenburg, 405 30 Gothenburg, Sweden.
Cancers (Basel). 2023 Jun 27;15(13):3362. doi: 10.3390/cancers15133362.
Women with ovarian cancer have limited therapy options, with immunotherapy being unsatisfactory for a large group of patients. Tumor cells spread from the ovary or the fallopian tube into the abdominal cavity, which is commonly accompanied with massive ascites production. The ascites represents a unique peritoneal liquid tumor microenvironment with the presence of both tumor and immune cells, including cytotoxic lymphocytes. We characterized lymphocytes in ascites from patients with high-grade serous ovarian cancer. Our data reveal the presence of NK and CD8 T lymphocytes expressing CD103 and CD49a, which are markers of tissue residency. Moreover, these cells express high levels of the inhibitory NKG2A receptor, with the highest expression level detected on tissue-resident NK cells. Lymphocytes with these features were also present at the primary tumor site. Functional assays showed that tissue-resident NK cells in ascites are highly responsive towards ovarian tumor cells. Similar results were observed in an in vivo mouse model, in which tissue-resident NK and CD8 T cells were detected in the peritoneal fluid upon tumor growth. Together, our data reveal the presence of highly functional lymphocyte populations that may be targeted to improve immunotherapy for patients with ovarian cancer.
卵巢癌女性的治疗选择有限，免疫疗法对一大群患者并不令人满意。肿瘤细胞从卵巢或输卵管扩散到腹腔，通常伴随着大量腹水的产生。腹水代表了一种独特的腹膜液体肿瘤微环境，其中存在肿瘤细胞和免疫细胞，包括细胞毒性淋巴细胞。我们对高级别浆液性卵巢癌患者腹水中的淋巴细胞进行了表征。我们的数据显示存在表达CD103和CD49a的自然杀伤细胞（NK）和CD8 T淋巴细胞，这两种分子是组织驻留的标志物。此外，这些细胞表达高水平的抑制性NKG2A受体，在组织驻留NK细胞上检测到的表达水平最高。具有这些特征的淋巴细胞也存在于原发肿瘤部位。功能分析表明，腹水中的组织驻留NK细胞对卵巢肿瘤细胞具有高度反应性。在体内小鼠模型中也观察到了类似结果，在该模型中，肿瘤生长时在腹水中检测到了组织驻留NK细胞和CD8 T细胞。总之，我们的数据揭示了存在高功能淋巴细胞群体，针对这些群体可能会改善卵巢癌患者的免疫治疗。
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