Abstract A102: The fat in ovarian cancer: Immune-dependent tumor-promoting effects

Abstract

Because of the particular anatomy of ovaries, which are in close contact with the adipocyte-rich omentum, ovarian cancer frequently presents itself with established metastasis-like disseminated tumor islets along the omentum. The tropism of ovarian cancer cells for fat is well described. Indeed, adipocyte-derived free fatty acids have been causatively linked to cancer cell proliferation and invasive properties. Obesity is additionally linked to increased risk of ovarian cancer onset and, in ovarian cancer patients, to worse outcome. However, there is to our knowledge no clear association between omentum-anchored dissemination and the anti-tumor immune response. Here we describe an unsuspected association between the presence peritoneal fat in ovarian tumors and massive tumor infiltration by T cells. Still, this massive T cell influx seems to fail in its anti-tumor activity since (1) tumor-infiltrating T cells seem to be hijacked away from tumor cells and accumulate around fatty areas and (2) tumor-infiltrating T cells display an exhausted phenotype. In this presentation, we also describe a new model of tissue culture of explants from primary human tumors that are treated with various drugs in an attempt to circumvent this fat-derived immune exhaustion and restore an efficient anti-tumor immune response. Citation Format: Meggy Suarez-Carmona, Anita Heinzelmann, Nektarios A. Valous, Mareike Hampel, Anna Berthel, Sarah Schott, Inka Zörnig, Dirk Jäger, Niels Halama. The fat in ovarian cancer: Immune-dependent tumor-promoting effects [abstract]. In: Proceedings of the Second CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; 2016 Sept 25-28; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(11 Suppl):Abstract nr A102.

Visceral abdominal fat measured by computer tomography as a prognostic factor for gynecological malignancies?

“…Previous investigations have shown that elevated inflammation markers, a sign of negative outcome in oncologic patients, are associated with decreased muscle mass but have no association with BMI [ 51 ]. Other studies investigating adipocyte-derived free fatty acids have shown a causative link to cancer cell proliferation and invasive properties, which might impact prognosis [ 52 ]. Such studies might lead to clinical recommendations, for example the earlier use of parenteral food to increase caloric intake and prevent the metabolomics switch.…”

The prognostic impact of myosteatosis on overall survival in gynecological cancer patients: A meta‐analysis and trial sequential analysis

“…Myocellular lipid accumulation promotes the secretion of several mediators (eg, inflammatory kinases and reactive oxygen species) or free fatty acids, which cause insulin resistance, activate cancer cell proliferation and invasiveness and impact prognosis. 48,49 Either intra-or extramyocellular adipose can change the shapes of muscle fibers, slow nutritive blood flowing to myocyte and impair the strength and velocity of muscle contraction, 48 which would eventually provide a broad area for tumors to spread, increase surgical blood loss and extend operation time. 50 Evidence inferred that cancer patients with myosteatosis are unlikely to achieve complete resection, 30 and consequently postoperative residuals will lead to a cancer relapse and treatment failure.…”

“…So far, metabolic disturbance and mechanical dysfunction of skeletal muscle have been recognized as the causes of the detrimental impacts of myosteatosis on survival. Myocellular lipid accumulation promotes the secretion of several mediators (eg, inflammatory kinases and reactive oxygen species) or free fatty acids, which cause insulin resistance, activate cancer cell proliferation and invasiveness and impact prognosis 48,49 . Either intra‐ or extramyocellular adipose can change the shapes of muscle fibers, slow nutritive blood flowing to myocyte and impair the strength and velocity of muscle contraction, 48 which would eventually provide a broad area for tumors to spread, increase surgical blood loss and extend operation time 50 .…”