Ovarian cancer is one of the most deadly gynecological cancers seen in women and is among the most challenging diseases in the medical world. This disease, which affects hundreds of thousands of women every year, is often diagnosed at an advanced stage and therefore responds late to treatment, significantly reducing survival rates. One of the main reasons for this situation is an advanced stage known as peritoneal carcinomatosis, where tumor cells spread to the intra-abdominal membranes. There is a remarkable actor in this spread: the omentum.
Although the omentum is defined as a membrane structure covered with fatty tissue that covers the intra-abdominal organs, it is a functionally active tissue that contains many elements related to the immune system. While the lymphoid structures called milky spots make it possible to think that this tissue plays an active role in immune defense, it is observed that it plays the opposite role in tumors such as ovarian cancer, facilitating the spread of cancer. This contradiction brings with it the question of whether the omentum is a friend or an enemy.
A new scientific publication that examines the opposing roles of the omentum in detail addresses the immunological and tumor-supporting functions of this structure and questions whether it is a potential target in the fight against ovarian cancer. According to the publication in question, although the omentum may seem like an immune area that will prevent tumor spread at first glance, in practice, cancer cells use this structure as a springboard and contribute to the spread of peritoneal carcinomatosis.
The milky spot structures in the omentum have functions such as antigen presentation, cytokine release and regulation of the immune response with their complex structures consisting of T and B lymphocytes, natural killer cells, macrophages and dendritic cells. However, in ovarian cancer, these immune structures cannot provide an effective defense against tumor cells, on the contrary, they create a tolerogenic environment that will allow these cells to settle.
In particular, the dominance of CD163+ Tim4+ macrophages in the omentum forms the basis of the immunosuppressive microenvironment. This macrophage subgroup prevents T-cell activation, facilitating the growth of tumor cells without being noticed. However, the dense vascular network and environmental signals of the omentum further facilitate the invasion and spread of tumor cells.
Another reason why the omentum is attractive to tumors is from a metabolic perspective. This region, filled with fatty tissue, provides an energy source for ovarian tumor cells. Tumor cells gain the ability to proliferate rapidly by using lipids taken from adipocytes in the omentum. This situation makes the omentum suitable for cancer not only in terms of microsystemic but also metabolic adaptation.
Another important feature of the omentum is that it is the primary settlement area in both transperitoneal spread and hematological (blood-borne) metastasis. Studies show that the omentum also attracts tumor cells coming from the bloodstream with specialized signals such as neuregulin-1 (NRG1). Ovarian tumor cells carrying the HER3 receptor perceive these signals and attach to the omentum and proliferate there.
Despite all this, the possibility that the omentum can also be used as a potential defense weapon has been a topic of discussion recently. It is suggested that immunotherapy strategies directed intraperitoneally (into the abdomen) in particular can create an anti-tumor response by activating milky spot structures. Experiments in mouse models have shown that the omentum has the capacity to create such specific responses.
In these experiments, it was observed that dendritic cells were activated in the omentum and both CD4+ and CD8+ T cells were specifically activated as a result of intraperitoneal injection of tumor cells killed with radiation. This shows that the omentum is actually a potential source of immune response and can be reprogrammed to fight tumors.
The use of the omentum as a defense mechanism includes not only T cells but also natural killer (NK) cells. It has been determined that NK cells are effective against both specific and non-specific tumors when activated in the omentum. This makes it possible to design new generation immunotherapy approaches such as CAR-T as omentum-targeted.
Of course, this double-sided structure of the omentum also affects surgical approaches. Although omentectomy (removal of the omentum), which has become almost standard in advanced ovarian cancer cases today, seems logical due to the tumor-supporting role of this tissue, it can actually mean the elimination of a potential immune defense center. Therefore, advanced biomarker analyses should be used to determine in which patient the omentum should be preserved.
The omentum can be both a metastatic nest and an immunological fortress. The direction in which it can be turned will be the focus of future immunotherapy strategies. Like a sword, it can save lives or cause death, depending on how it is used.
Subject of Research: Immunological and metastatic functions of the omentum in ovarian cancer
Article Title: Omentum: Friend or foe in ovarian cancer immunotherapy?
News Publication Date: April 2, 2025
Web References: https://doi.org/10.1016/bs.ircmb.2022.04.017
References: Bella A., Arrizabalaga L., Di Trani C.A., et al. (2022). Omentum: Friend or foe in ovarian cancer immunotherapy? International Review of Cell and Molecular Biology, 371, 117–131.
Keywords: Ovarian cancer, omentum, peritoneal carcinomatosis, milky spots, CD163+ Tim4+ macrophage, immunotherapy, metastasis, HER3, NRG1, CAR-T, TGF-β, VEGF, Treg, CD8+ T cell, NK cell, immunosuppression
Tags: advanced stage cancer treatmentcancer research publicationsgynecological cancer survival ratesimmune system and ovarian cancerimmunological roles of the omentumintra-abdominal membrane functionsmilky spots functionomentum as tumor facilitatoromentum friend or enemyomentum in cancer spreadovarian cancer diagnosis challengesperitoneal carcinomatosis role
