Acosta Jasmin C, Bahr Janice M, Basu Sanjib, O'Donnell James T, Barua Animesh
Department of Anatomy and Cell Biology, Rush University Medical Center, Chicago, IL 60612, USA.
Department of Animal Science, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
Biomedicines. 2023 Jan 21;11(2):299. doi: 10.3390/biomedicines11020299.
Epithelial ovarian cancer (OVCA), a fatal malignancy of women, disseminates locally. Although NK cells mount immune responses against OVCA, tumors inhibit NK cells, and the mechanism is not well understood. Cytokines stimulate NK cells; however, chronic stimulation exhausts them and induces expression of cytokine-inducible SH2-containing protein (CISH). Tumors produce anti-inflammatory cytokine interleukin (IL)-10 which may induce NK cell exhaustion. The goal of this study was to examine if CISH expression in NK cells increases during OVCA development and to determine the mechanism(s) of OVCA-induced CISH expression in NK cells. Normal ovaries ( = 7) were used for CISH, IL-10 and GRP78 expression. In tumor ovaries, CISH was examined in early and late stages ( = 14 each, all subtypes) while IL-10 and GRP78 expression were examined in early and late stage HGSC ( = 5 each). Compared to normal, the population of CISH-expressing NK cells increased and the intensity of IL-10 and GRP78 expression was significantly higher in OVCA ( < 0.05). CISH expression was positively correlated with IL-10 expression (r = 0.52, r = 0.65, < 0.05 at early and late stages, respectively) while IL-10 expression was positively correlated with GRP78 expression (r = 0.43, r = 0.52, < 0.05, respectively). These results suggest that OVCA development and progression are associated with increased CISH expression by NK cells which is correlated with tumor-induced persistent cellular stress.
上皮性卵巢癌（OVCA）是一种致命的女性恶性肿瘤，可在局部扩散。尽管自然杀伤（NK）细胞会对OVCA发起免疫反应，但肿瘤会抑制NK细胞，其机制尚不清楚。细胞因子可刺激NK细胞；然而，长期刺激会使它们耗竭并诱导细胞因子诱导的含SH2蛋白（CISH）的表达。肿瘤会产生抗炎细胞因子白细胞介素（IL）-10，它可能会诱导NK细胞耗竭。本研究的目的是检查在OVCA发展过程中NK细胞中CISH的表达是否增加，并确定OVCA诱导NK细胞中CISH表达的机制。使用正常卵巢（n = 7）检测CISH、IL-10和GRP78的表达。在肿瘤卵巢中，检测早期和晚期（各14例，所有亚型）的CISH，而在早期和晚期高级别浆液性癌（HGSC）中检测IL-10和GRP78的表达（各5例）。与正常情况相比，OVCA中表达CISH的NK细胞群体增加，IL-10和GRP78的表达强度显著更高（P < 0.05）。CISH表达与IL-10表达呈正相关（早期和晚期的r分别为0.52和0.65，P < 0.05），而IL-10表达与GRP78表达呈正相关（r分别为0.43和0.52，P < 0.05）。这些结果表明，OVCA的发展和进展与NK细胞中CISH表达增加有关，这与肿瘤诱导的持续性细胞应激相关。
