An Increased Abundance of Tumor-Infiltrating Regulatory T Cells Is Correlated with the Progression and Prognosis of Pancreatic Ductal Adenocarcinoma

“…In hepatocellular carcinoma (HCC) and pancreatic cancer, accumulation of Treg has been directly associated with poor prognosis. 22,[26][27][28] Little is known so far about the mechanisms leading to CCL22 expression in the cancer tissue. In our study, we show that tumor cell-derived IL-1a specifically induces CCL22 expression in tumor-infiltrating dendritic cells.…”

Section: Introductionmentioning

confidence: 99%

Cancer cell-derived IL-1α induces CCL22 and the recruitment of regulatory T cells

et al. 2016

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In cancer patients, immunosuppression through regulatory T cells (Treg) is a crucial component of tumor immune evasion and contributes to disease progression. Tumor-infiltrating Treg in particular suppress local effector T cell responses and are associated with poor prognosis in tumors such as human pancreatic cancer or hepatocellular carcinoma (HCC). The chemokine CCL22 is known to recruit Treg into the tumor tissue and many types of human tumors are known to express high levels of CCL22. The mechanisms leading to intratumoral secretion of CCL22 are so far unknown. We demonstrate here that intratumoral CCL22 is induced in tumor-infiltrating immune cells through cancer cell-derived interleukin-1 (IL-1a). In pancreatic cancer and HCC, CCL22 is produced by intratumoral dendritic cells, while the cancer cells themselves do not secrete CCL22 in vitro and in vivo. Incubation of human peripheral blood mononuclear cells (PBMC) or murine splenocytes with tumor cells or tumor cell supernatants strongly induced CCL22 secretion in vitro. Tumor cell supernatants contained IL-1 and CCL22 induction in PBMC could be specifically prevented by the IL-1 receptor antagonist anakinra or by transfection of tumor cell lines with IL-1 siRNA, leading to a suppression of Treg migration. In conclusion, we identify here tumor cell-derived IL-1a as a major inducer of the Treg attracting chemokine CCL22 in human cancer cells. Therapeutic blockade of the IL-1 pathway could represent a promising strategy to inhibit tumorinduced immunosuppression.

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“…Therefore, it is likely that decreased numbers of those cells is associated with impairment of immunity against tumors, which results in tumor progression. In fact, several studies have demonstrated that the numbers of tumor infiltrating lymphocytes, such as CD4 + and CD8 + T cells, were associated with prognosis in some cancers [16-18]. Furthermore, a close correlation between decreased numbers of immune cells, such as NK cells, B cells, and gamma-delta T cell, and poor prognosis has also been demonstrated in both peripheral blood and cancer tissue for some cancer types [19-21].…”

Section: Discussionmentioning

confidence: 99%

Prognostic Significance of Pre- and Postoperative Lymphocyte Counts in Patients with Gastric Cancer

et al. 2018

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Background: Although preoperative lymphopenia is reportedly a prognostic factor in cancer patients, the association between postoperative lymphopenia and patient prognosis has not been widely studied. Methods: We enrolled 352 patients who underwent surgery for gastric cancer (GC) between January 2005 and April 2013 to analyze correlations among pre- and postoperative lymphocyte counts (LCs) and prognosis in GC patients. Results: Pre- and postoperative (obtained 1 day after surgery) LCs were significantly correlated (r = 0.496, p < 0.0001). Pre- and postoperative LCs of elderly patients were significantly lower than those of non-elderly patients. Postoperative lymphocyte count was significantly lower in patients with a differentiated tumor than in those with an undifferentiated tumor. Based on the results of receiver operating characteristic analysis, patients were classified into subgroups as: preoperative LC ≥1,676 (pre-LC^High), preoperative LC <1,676 (pre-LC^Low); and as postoperative LC ≥855 (post-LC^High), and postoperative LC <855 (post-LC^Low). Five-year overall survival rates significantly differed between pre-LC^High (82.5%) and pre-LC^Low (71.6%) groups (p = 0.023); and also between the post-LC^High (81.5%) and post-LC^Low (69.5%) groups (p = 0.0072). The 5-year disease specific survival rates were 91.3 and 82.4% in patients with post-LC^High and those with post-LC^Low, respectively, and differences were statistically significant (p = 0.015). Multivariate analysis indicated that postoperative lymphocyte count was an independent prognostic indicator, along with age, gender, tumor size, lymph node metastasis, and venous invasion. Conclusions: Postoperative lymphocyte count is a useful predictive factor for prognosis in GC patients.

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An Increased Abundance of Tumor-Infiltrating Regulatory T Cells Is Correlated with the Progression and Prognosis of Pancreatic Ductal Adenocarcinoma

Cited by 189 publications

References 45 publications

High expression of sphingosine kinase 1 is associated with poor prognosis in nasopharyngeal carcinoma

High expression of sphingosine kinase 1 is associated with poor prognosis in nasopharyngeal carcinoma

Cancer cell-derived IL-1α induces CCL22 and the recruitment of regulatory T cells

Prognostic Significance of Pre- and Postoperative Lymphocyte Counts in Patients with Gastric Cancer

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