NK cells are a major component of the antitumour immune response that limits tumour progression. However, it has been reported that tumour-infiltrating NK (TINK) cells from patients with non-small-cell lung carcinoma (NSCLC) exhibit profound defects in degranulation and IFN-γ production. In support of this notion, we report a novel mechanism associated with tumour escape from NK cell-mediated antitumour immunity in lung carcinoma. In this study, we investigated the phenotypic profile of TINK cells based on the expression of the NK-cell maturation markers CD11b and CD27. Interestingly, we found a substantial CD11b−CD27− (DN) NK-cell population harboured within the tumour tissues. The presence of this CD11b−CD27− NK subset indicated that the TINK cells were of an immature and inactive phenotype. Remarkably, we determined that the presence of DN NK cells had an impact on the clinical outcomes of patients with NSCLC, as the frequency of tumour-infiltrating DN NK cells was positively correlated with the tumour stage and tumour size. We further used a murine Lewis lung cancer (LLC) model to confirm the correlation between the frequency of tumour-infiltrating DN NK cells and the progression of lung carcinoma. Together, our findings demonstrate that the tumour microenvironment may render TINK cells less tumouricidal and thereby contribute to cancer progression.
Esophageal cancer (EC) is one of the most common mucosa-associated tumors, and is characterized by aggressiveness, poor prognosis, and unfavorable patient survival rates. As an organ directly exposed to the risk of foodborne infection, the esophageal mucosa harbors distinct populations of innate immune cells, which play vital roles in both maintenance of esophageal homeostasis and immune defense and surveillance during mucosal anti-infection and anti-tumor responses. In this review, we highlight recent progress in research into innate immune cells in the microenvironment of EC, including lymphatic lineages, such as natural killer and γδT cells, and myeloid lineages, including macrophages, dendritic cells, neutrophils, myeloid-derived suppressor cells, mast cells and eosinophils. Further, putative innate immune cellular and molecular mechanisms involved in tumor occurrence and progression are discussed, to highlight potential directions for the development of new biomarkers and effective intervention targets, which can hopefully be applied in long-term multilevel clinical EC treatment. Fully understanding the innate immunological mechanisms involved in esophageal mucosa carcinogenesis is of great significance for clinical immunotherapy and prognosis prediction for patients with EC.
Small cell carcinoma of the esophagus (SCCE) is a rare, highly aggressive tumor characterized by early dissemination and a poor prognosis. Surgery, chemotherapy, and radiotherapy have been used alone or in combination for the treatment of this rare disease. The aim of this retrospective study was to analyze the role of surgery in the management of limited-stage SCCE at a high-volume center. We retrospectively evaluated 73 patients with limited-stage SCCE who received an esophagectomy at our center from January 1994 to December 2011. The clinical characteristics, median survival times (MSTs), overall survival (OS), and relevant prognostic factors were analyzed. The overall MST was 23.0 months, and the 1-, 2-, 3-, and 5-year OS rates were 61.6%, 47.9%, 22.7%, and 10.6%, respectively. The MST for patients without lymph node involvement (33.0 months) was greater than the MST for patients with lymph node involvement (17.0 months) (P = 0.014). Similarly, patients who underwent radical resection had a greater MST (25.0 months) than patients who underwent palliative resection (7.0 months) (P = 0.004). Patients who received chemotherapy had a greater MST (27.0 months) than patients who did not receive chemotherapy (13.0 months) (P = 0.021). Survival analysis confirmed that a radical operation, chemotherapy, and lymph node involvement were independent prognostic factors. This study suggests that radical resection combined with chemotherapy should be recommended for patients with limited-stage SCCE, especially patients with negative regional lymph nodes. A lack of lymph node metastasis was a good prognostic factor because patients without lymph node involvement had greater OS.
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