Background: NKG2A is an inhibitory receptor of both T cells and natural killer (NK) cells. Persistent activation promotes T cells and NK cells to express NKG2A and results in the progression of chronic infection and cancer. However, the characteristics and subsets of NKG2A + lymphocytes in human lung cancer are still unclear.Methods: Here, we used the Tumor Immune Estimation Resource database and immune profiling of paired biospecimens to uncover the correlation between NKG2A expression and immune infiltration levels in human cancer as well as the characteristics of NKG2A + lymphocytes in human lung cancer.Results: We found that KLRC1 expression was especially correlated with CD8 + T-cell infiltration levels in 34 types of human cancer through the Tumor Immune Estimation Resource database. Moreover, NKG2A + CD8 + T cells were the predominant subset of NKG2A + lymphocytes in human lung cancer. In contrast, the NKG2A + NK cells were decreased in tumors compared with the paired normal lung tissue. Tumor-infiltrating NKG2A + CD8 + T cells expressed tissue-resident memory T cell (T RM cell) and exhausted T-cell markers. Cytokines and cytotoxic molecules secreted by tumor-infiltrating NKG2A + CD8 + T cells were significantly lower than those secreted by NKG2A − CD8 + T cells in vitro. When stimulated with T-cell receptor activator, tumor-infiltrating NKG2A + CD8 + T cells could secrete large amounts of granzyme B.Conclusions: Our findings demonstrate that tumor-infiltrating NKG2A + CD8 + T cells form the predominant subset of NKG2A + cells in human lung cancer and suggest that targeting NKG2A + CD8 + T cells is a promising approach for future anti-lung cancer immunotherapy.

BackgroundCentrosomal protein 55 (CEP55) is an important prognostic biomarker that plays an essential role in the proliferation, migration and invasion of multiple tumors. We aimed to investigate the prognostic value of CEP55 in pN0 esophageal squamous cell carcinoma (ESCC) and explore its biological function in ESCC cells.MethodsWe used immunohistochemistry and Western blot analysis to detect the expression of CEP55 in ESCC. Furthermore, both in vitro and in vivo assays were used to determine the effect of CEP55 on malignant behavior in ESCC cells.ResultsAs expected, we found that CEP55 was overexpressed in ESCC. Univariate and multivariate analyses demonstrated that patients with CEP55 overexpression had a poor prognosis. Additionally, the abilities of proliferation, migration and invasion of cells, as well as the epithelial–mesenchymal transition markers, were all altered with the changed CEP55 expression levels in ESCC cells. Further study elucidated that CEP55 facilitated ESCC via the PI3K/Akt pathway. Blockade of this pathway markedly attenuated CEP55-mediated proliferation, migration, invasion and epithelial–mesenchymal transition of ESCC cells.ConclusionOncogenic CEP55 correlates with a poor prognosis by regulating tumor cell proliferation, migration and invasion via the PI3K/Akt pathway. It can serve as a promising prognostic biomarker and therapeutic target of pN0 ESCC after Ivor-Lewis esophagectomy.

BackgroundThe FGFR family can be activated by FGFs and plays important roles in regulating cell growth, differentiation, migration, and angiogenesis. Recent studies have suggested that FGFR4 could regulate several processes, including tumor progression. Esophageal squamous cell carcinoma (ESCC) is a malignancy with high global occurrence. However, the molecule mechanism and the potential roles of FGFR4 in ESCC remain unknown.MethodsImmunohistochemistry and Western blotting were used to detect FGFR4 expression in ESCC samples and cell lines. Cell counting kit‐8, and clonogenic, transwell, flow cytometric, and tumor xenograft in nude mice assays were utilized to determine the effect of blocking FGFR4 in proliferation, invasion, migration, and apoptosis of ESCC cells.ResultsFGFR4 is frequently overexpressed in ESCC tissue and cell lines. in vitro assays have shown that blocking FGFR4 by a specific blocker, H3B‐6527, significantly decreases proliferation, invasion, and migration, and alters epithelial‐mesenchymal transition markers in ESCC cells. In addition, FGFR4 blockade is associated with the induction of apoptosis and affects PI3K/Akt and MAPK/ERK pathways. Moreover, FGFR4 blockade could significantly inhibit the growth of xenograft tumors in vivo.ConclusionOur findings suggest that blocking FGFR4 significantly suppresses the malignant behaviors of ESCC and indicate that FGFR4 is a potential target for the treatment of ESCC.

Esophageal squamous cell carcinoma (ESCC) is one of the most common digestive tumors worldwide. The Mucin 1 (MUC1) heterodimeric protein has been confirmed that is overexpressed in ESCC and induced adverse outcomes. However, the detailed mechanism(s) remained challenging. So, we investigated the relationship between MUC1‐C and metabolism in ESCC cells. In the results, TP53‐induced glycolysis and apoptosis regulator (TIGAR) was overexpressed and correlative with MUC1‐C positively in ESCC tissue. Targeting MUC1‐C inhibits AKT–mTORC–S6K1 signaling and blocks TIGAR translation. We found that the inhibitory effect of GO‐203 on TIGAR was mediated by inhibition of AKT–mTOR–S6K1 pathway. The findings also demonstrated that the suppressive effect of GO‐203 on TIGAR is related to the decrease of glutathione level, the increase of reactive oxygen species and the loss of mitochondrial transmembrane membrane potential. In xenograft tissues, GO‐203 inhibited the growth of ESCC cells and lead to the low expression of transmembrane C‐terminal subunit (MUC1‐C) and TIGAR. This evidence supports the contention that MUC1‐C is significant for metabolism in ESCC and indicated that MUC1‐C is a potential target for the treatment of ESCC.