Program of Immunology and Immunotherapy, Cima Universidad de Navarra, Pamplona, Spain; Navarra Institute for Health Research (IdiSNA), Pamplona, Spain.
Program of Immunology and Immunotherapy, Cima Universidad de Navarra, Pamplona, Spain; Navarra Institute for Health Research (IdiSNA), Pamplona, Spain.
Int Rev Cell Mol Biol. 2022;371:117-131. doi: 10.1016/bs.ircmb.2022.04.017. Epub 2022 Jun 27.
Ovarian cancer often spreads out of the ovary before a patient is diagnosed and is the deadliest gynecological malignancy. The aggressiveness of ovarian cancer is determined by the progression in the form of peritoneal carcinomatosis, a stage with a poor prognosis and an untreatable condition in most patients. One of the first tumor nests or the origin of metastasis in the peritoneal cavity is the omentum. The omentum contains immune aggregates, called milky spots, embedded in adipose tissue, which support tumor growth by various mechanisms, including immunosuppressive immune cells and metabolic functions. In this sense, the abundance of blood vessels, omental resident macrophages, and chemokines, among other factors, are known to promote invasiveness, proliferation and resistance to cancer therapies. As a result, surgical practice employed in advanced-stage ovarian cancer almost constantly includes omentectomy. Paradoxically, the omentum is considered the "abdominal policeman" that contributes to peritoneal immunity by capturing antigens and pathogens from the peritoneal cavity and promoting effective immune responses against microbes. Why immunosurveillance against the metastatic tumor does not take place in the omentum? Could omental immune responses be activated with immunotherapeutic interventions? The omentum has largely been ignored in cancer immunology and immunotherapy, and the potential translational implications of this in ovarian cancer are still unclear. Here, we focus on the dual role of the omentum in ovarian cancer: its role in antitumor immune responses versus its activities fostering cancer progression.
卵巢癌在患者被诊断之前往往已经扩散到卵巢外，是最致命的妇科恶性肿瘤。卵巢癌的侵袭性由腹膜癌病的进展决定，这是一个预后不良的阶段，大多数患者的病情无法治疗。腹膜腔中第一个肿瘤巢或转移的起源之一是大网膜。大网膜包含免疫聚集物，称为乳斑，嵌入脂肪组织中，通过各种机制支持肿瘤生长，包括免疫抑制性免疫细胞和代谢功能。从这个意义上说，血管、网膜固有巨噬细胞和趋化因子等因素的丰富程度已知可促进侵袭性、增殖和对癌症治疗的耐药性。因此，在晚期卵巢癌中采用的手术实践几乎总是包括网膜切除术。矛盾的是，大网膜被认为是“腹部警察”，通过从腹腔中捕获抗原和病原体并促进对微生物的有效免疫反应，有助于腹膜免疫。为什么针对转移性肿瘤的免疫监视不会发生在大网膜中？免疫治疗干预能否激活网膜免疫反应？网膜在癌症免疫学和免疫治疗中基本上被忽视了，其在卵巢癌中的潜在转化意义尚不清楚。在这里，我们重点关注大网膜在卵巢癌中的双重作用：它在抗肿瘤免疫反应中的作用与促进癌症进展的作用。
