P129 Assessment of cytokine mRNA expression profiles in tumor microenvironment and peripheral blood mononuclear cells of patients with high-grade serous carcinoma of the ovary

Israelsson, Pernilla; Labani‐Motlagh, Alireza; Nagaev, Ivan; Dehlin, Eva; Nagaeva, Olga; Lundin, Eva; Ottander, Ulrika; Mincheva‐Nilsson, Lucia

doi:10.1136/ijgc-2019-esgo.191

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“… 36 We have no information on the architecture of the TME and of the individual tumors, such as difference in resident cells, genomic changes in the HGSC cells and other immunosuppressive mechanisms operating at the same time. 7 , 14 , 18 It is interesting to observe that when we tested the cytotoxic capacity of the patients’ own NK cells before and after surgery, we found that their cytotoxic potential was enhanced postoperatively in both groups, although more prominent in Group 1 patients (Figure 4 ).…”

Section: Discussionmentioning

confidence: 89%

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NKG2D‐mediated cytotoxicity improves after primary surgery for high‐grade serous ovarian cancer

Israelsson

Björk

Nagaev

et al. 2022

American J Rep Immunol

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Problem Tumors compromise the patients’ immune system to promote their own survival. We have previously reported that HGSC exosomes play a central role, downregulating NKG2D cytotoxicity. Primary surgery's effect on tumor exosomes and NKG2D cytotoxicity in HGSC patients has not been studied before. The overall objective of this study was to explore the effect of surgery on the exosome‐induced impairment of NKG2D cytotoxicity in HGSC. Method of study Paired pre‐ and post‐operative blood samples were subjected to cell and exosome analyses regarding the NKG2D receptor and ligands, and NKG2D‐mediated cytotoxicity. Lymphocytes were phenotyped by immunoflow cytometry. Exosomes, isolated by ultracentrifugation, and characterized by nanoparticle tracking analysis, transmission and immune electron microscopy and western blot were used in functional cytotoxic experiments. HGSC explant culture‐derived exosomes, previously studied by us, were used for comparison. Results HGSC exosomes from patients’ sera downregulated NKG2D‐mediated cytotoxicity in NK cells of healthy donors. In a subgroup of subjects, NKG2D expression on CTLs and NK cells was upregulated after surgery, correlating to a decrease in the concentration of exosomes in postoperative sera. An overall significantly improved NKG2D‐mediated cytotoxic response of the HGSC patients’ own NK cells in postoperative compared to preoperative samples was noted. Conclusions Surgical removal of the primary tumor has a beneficial effect, relieving the exosome‐mediated suppression of NKG2D cytotoxicity in HGSC patients, thus boostering their ability to combat cancer.

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Section: Discussionmentioning

confidence: 89%

“… 6 We have previously reported that the cytokine mRNA profile in the HGSC TME is dominated by immunoinhibitory and pro‐inflammatory cytokines, favoring tumor survival and spread. 7 …”

Section: Introductionmentioning

confidence: 99%