Peritoneal ascites are a distinguishable feature of patients with advanced epithelial ovarian cancer (EOC). The presence of different lymphocyte subsets has been reported in EOC-associated ascites, which also can or not contain malignant cells. The goal of this study was to analyze the functional characteristics of natural killer (NK) cells from EOC-associated ascites in terms of their expression of activating receptors and ascites’ contents of lymphocyte subtypes, cytokine profile and presence of EOC cells. NK cell function was evaluated by the expression of the degranulation marker CD107a in resting and interleukin (IL)-2 stimulated NK cells from ascites and blood. Degranulation of NK cells from EOC cell-free ascites was significantly (p < 0.05) higher than all the other groups, either in their resting state or after IL-2 stimulation, suggesting a previous local stimulation. In contrast, treatment with IL-2 had no effect on NK cells from ascites with EOC cells. The amount of regulatory T cells was significantly higher in ascites with EOC cells compared to EOC cell-free ascites. Ascites with EOC cells also had higher levels of tumor necrosis factor (TNF)-α, suggesting inflammation related to the malignancy. In conclusion, the functional performance of NK cells was distinct between EOC cell-free ascites and ascites with EOC cells. The impairment of NK cell response to IL-2 in ascites with EOC cells was consistent with an immunosuppressive tumor microenvironment.

The spontaneous immortalization of primary malignant cells is frequently assigned to their genetic instability during in vitro culturing. In this study, the new epithelial ovarian cancer cell line CAISMOV24 was described and compared with its original low-grade serous ovarian carcinoma. The in vitro culture was established with cells isolated from ascites of a 60-year-old female patient with recurrent ovarian cancer. The CAISMOV24 line was assessed for cell growth, production of soluble biomarkers, expression of surface molecules and screened for typical mutations found in serous ovarian carcinoma. Additionally, comparative genomic hybridization was employed to compare genomic alterations between the CAISMOV24 cell line and its primary malignant cells. CAISMOV24 has been in continuous culture for more than 30 months and more than 100 in vitro passages. The cell surface molecules EpCAM, PVR and CD73 are overexpressed on CAISMOV24 cells compared to the primary malignant cells. CAISMOV24 continues to produce CA125 and HE4 in vitro. Although the cell line had developed alongside the accumulation of genomic alterations (28 CNV in primary cells and 37 CNV in CAISMOV24), most of them were related to CNVs already present in primary malignant cells. CAISMOV24 cell line harbored KRAS mutation with wild type TP53, therefore it is characterized as low-grade serous carcinoma. Our results corroborate with the idea that genomic alterations, depicted by CNVs, can be used for subtyping epithelial ovarian carcinomas. Additionally, CAISMOV24 cell line was characterized as a low-grade serous ovarian carcinoma, which still resembles its primary malignant cells.

Killer cell immunoglobulin-like receptors (KIR) exhibit extensive diversity, giving rise to different KIR profiles in populations worldwide. This study aimed to investigate the distribution of KIR genes and HLA ligands in a population from Campinas, southeastern Brazil (n = 292), and to compare their results with other populations. A comprehensive analysis of population-specific genes, genotype, and haplotype frequencies of KIR may facilitate a better understanding of their evolution and role in immunity. The genotyping of 16 KIR genes and HLA class I alleles was performed by the reverse sequence-specific oligonucleotide methodology using the Luminex platform (One Lambda, Inc., Canoga Park, CA). The framework genes were present in all individuals, with the most common non-framework KIR genes detected being KIR2DP1(96.6%), KIR2DL1(95.5%), KIR3DL1(94.5%), KIR2DS4(93.8%) and KIR2DL3(87.3%). KIR2DS1, KIR2DS3, KIR2DS5, and KIR3DS1 presented frequencies below 40%. KIR2DL2, KIR2DL5, and KIR2DS2 showed intermediate frequencies (between53% and 58%). The activating gene KIR2DS5 was the least common in this population (30.8%). Forty-five KIR profiles were found with the commonest being the homozygous A haplotype (27.4%). The distribution of KIR genes in the Brazilian population is similar to Caucasian European and Euro-descendant populations.

NK cells are cytotoxic lymphocytes, representing about 5–15% of circulating mononuclear lymphocytes, and are defined as CD3-CD56 + NKp46+. They play crucial roles in host defense by recognizing and eliminating virus-infected and tumor cells without prior sensitization. The function of NK cells is regulated by a repertoire of receptors that issue activating or inhibitory intracellular signals. The ligands for these receptors can be diverse. Recent studies show that interactions between NK cell receptors and their ligands can depend on the peptide presented by HLA at the time. This chapter explores key findings in the literature regarding the interaction between NK cell receptors, HLA, and peptides and aims to understand the immunological mechanisms involved in these interactions and how these interactions might impact hematopoietic stem cell transplantation.

Natural killer (NK) cells are important lymphocytes of the innate immune response against cancer. Based on their molecular and functional phenotypes, NK cells are categorized into two main subtypes known as CD56 ^dim and CD56 ^bright , which display distinct transcriptional profiles. Additionally, transcriptomic alterations may arise in response to different stimuli or microenvironmental conditions, ultimately affecting NK‐cell functions. Here, RNA sequencing (RNAseq) was performed to characterize the transcriptomic profile of NK cells from epithelial ovarian cancer (EOC)‐associated ascites. Two bulk RNAseq datasets were analyzed: one generated from samples collected from patients assisted at the Women's Hospital of the University of Campinas (CAISM‐Unicamp, Brazil) and a second publicly available dataset obtained from the Gene Expression Omnibus database (GSE153713). Our transcriptomic analysis identified 5427 differentially expressed genes (DEGs; adjusted p < 0.05), revealing extensive differences between ascites and blood NK cells. Furthermore, these findings indicated a possible shift in the biological program of ascites NK cells, from the conventional cytotoxic CD16 ⁺ CD56 ^dim subtype to an immature/secretory CD56 ^bright profile. Comparison of ascites and blood NK RNAseq based on a previously defined transcriptional framework showed reduced NK1 and increased NK2 subtype scores in ascites, confirming association with distinct biological programs. In conclusion, ascites NK cells retain elements of the conventional NK‐cell program while displaying a transcriptional profile distinct from peripheral blood NK cells, consistent with transcriptional remodeling to biological programs usually associated with the CD56 ^bright NK subtype.