Altered CD94/NKG2A and perforin expression reduce the cytotoxic activity in malignant pleural effusions

Pace, Elisabetta; Sano, Caterina Di; Ferraro, Maria; Tipa, Annalisa; Olivieri, Dario; Spatafora, Mario; Santagata, Roberta; Bellia, Vincenzo; Gjomarkaj, Mark

doi:10.1016/j.ejca.2010.09.001

Cited by 13 publications

(15 citation statements)

References 30 publications

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“…Interestingly, we found that a high density of CD8+ IEL‐TIL was associated with an improved DFS, as already reported in previous studies 32–35. In fact, our results extend and deepen these previous findings.…”

Section: Discussionsupporting

confidence: 91%

HLA‐E/β2 microglobulin overexpression in colorectal cancer is associated with recruitment of inhibitory immune cells and tumor progression

Bossard

Bézieau

Matysiak‐Budnik

et al. 2012

Intl Journal of Cancer

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The host immune response plays a major role in colorectal carcinoma (CRC) progression. A mechanism of tumor immune escape might involve expression of the human leucocyte antigen (HLA)-E/b2m on tumor cells. The inhibitory effect of HLA-E/ b2m on CD81 cytotoxic T lymphocytes and natural killer (NK) cells is mediated by the main HLA-E receptor CD94/NKG2A. As the pathophysiological relevance of this mechanism in CRC remains unknown, this prompted us to examine, in situ, in a series of 80 CRC (i) the HLA-E and b2m coexpression by tumor cells, (ii) the density of CD81, cytotoxic, CD2441 and NKP461 intraepithelial tumor-infiltrating lymphocyte (IEL-TIL) and (iii) the expression of CD94/NKG2 receptor on IEL-TIL. These data were then correlated to patient survival. We provided (i) the in situ demonstration of HLA-E/b2m overexpression by tumor cells in 21% of CRC characterized by an overrepresentation of signet ring cell carcinomas, mucinous carcinomas and medullary carcinomas, (ii) the significant association between HLA-E/b2m overexpression by tumor cells and increased density of CD81 cytotoxic, CD2441 and CD941 IEL-TIL and (iii) finally, the unfavorable prognosis associated with HLA-E/b2m overexpression by tumor cells. Our findings show that HLA-E/b2m overexpression is a surrogate marker of poor prognosis and point to a novel mechanism of tumor immune escape in CRC in restraining inhibitory IEL-TIL.

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Section: Discussionsupporting

confidence: 91%

HLA‐E/β2 microglobulin overexpression in colorectal cancer is associated with recruitment of inhibitory immune cells and tumor progression

Bossard

Bézieau

Matysiak‐Budnik

et al. 2012

Intl Journal of Cancer

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“…Relative to this, MPE is characterised by defective recruitment, activation and the cytotoxic potential of CD8 + cells [22,23]. Macrophages from malignant effusions not only display reduced cytotoxic activity against autologous tumour cells but they also inhibit tumour cell apoptosis [24,25].…”

Section: Pathophysiology Of Mpementioning

confidence: 99%

Malignant pleural effusion: from bench to bedside

et al. 2016

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Malignant pleural effusion (MPE) is a common but serious condition that is related with poor quality of life, morbidity and mortality. Its incidence and associated healthcare costs are rising and its management remains palliative, with median survival ranging from 3 to 12 months. During the last decade there has been significant progress in unravelling the pathophysiology of MPE, as well as its diagnostics, imaging, and management. Nowadays, formerly bed-ridden patients are genotyped, phenotyped, and treated on an ambulatory basis. This article attempts to provide a comprehensive overview of current advances in MPE from bench to bedside. In addition, it highlights unanswered questions in current clinical practice and suggests future directions for basic and clinical research in the field. @ERSpublications This review provides up to date knowledge for malignant pleural effusion covering aspects from bench to bedside http://ow.ly/10w7vN

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“…TIGIT was reported to decrease NK cell-mediated killing of CD155-expressing cells in both humans and mice [14, 29, 30]. As reported in several articles, the expression of inhibitory receptors, such NKG2A [31] and KIR3DL1 [21], on NK cells usually increases in different cancers. However, in this study, we did not find differences between TIGIT expression in PC patients and healthy controls.…”

Section: Discussionmentioning

confidence: 99%

Altered expression of CD226 and CD96 on natural killer cells in patients with pancreatic cancer

Peng

Zhu

et al. 2016

Oncotarget

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The progression of pancreatic cancer (PC) is significantly associated with tumor immune escape, which may be associated with nature killer (NK) cell dysfunction. CD226, CD96, and TIGIT, which share the ligand CD155, play important roles in the regulation of NK cell function. The present study was conducted to investigate the roles of these molecules in NK cells from PC patients. Expression of these molecules on NK cells was detected from samples of 92 pancreatic cancer patients and 40 healthy controls. The expression of CD155 was also evaluated by immunohistochemistry in 88 pancreatic cancer tissues. The percentage of CD226+ and CD96+ NK cells was significantly lower in PC patients than in the healthy controls; however, the mean fluorescence intensity of CD226 and CD96 was not significantly different between the two groups. TIGIT expression on NK cells from PC patients was similar to that in the healthy controls. Additionally, the expression of CD226 was positively correlated with CD96. Further analysis demonstrated that the decrease in the percentage of CD226+ and CD96+ NK cells was associated with tumor histological grade and lymph node metastasis. Moreover, the CD155 levels in PC tissues were significantly higher than those in adjacent tissues. Our results suggest that a lower percentage of CD226+ and CD96+ NK cells may contribute to tumor immune escape in PC patients; moreover, the use of NK cells with high CD226 and CD96 expression to treat PC cells with high CD155 expression may have potential and should be explored in the future.

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Altered CD94/NKG2A and perforin expression reduce the cytotoxic activity in malignant pleural effusions

Cited by 13 publications

References 30 publications

HLA‐E/β2 microglobulin overexpression in colorectal cancer is associated with recruitment of inhibitory immune cells and tumor progression

HLA‐E/β2 microglobulin overexpression in colorectal cancer is associated with recruitment of inhibitory immune cells and tumor progression

Malignant pleural effusion: from bench to bedside

Altered expression of CD226 and CD96 on natural killer cells in patients with pancreatic cancer

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