An analysis of the immunological tumor microenvironment of primary tumors and regional lymph nodes in squamous cell lung cancer.

BACKGROUND: Various immune cells that play a central role in antitumor immunity accumulate in primary tumors and regional lymph nodes. Such cellular accumulation and the molecular expression were analyzed to elucidate the immunological tumor microenvironment. METHODS: Fifty squamous cell lung cancer patients with complete resection were included. Resected specimens from primary lung tumors and regional lymph nodes were immunostained for immune-related molecules, such as CD8, CD103, major histocompatibility complex (MHC) class I, and programmed cell death protein ligand-1 (PD-L1), and the relationship between the prognosis and clinicopathological factors was retrospectively analyzed. RESULTS: Tumor-infiltrating lymphocytes and CD8+ lymphocytes, intratumoral and intrastromal CD103+ lymphocytes, tumor diameter, pathological T and N factors, and pathological stage were significant prognostic factors for the disease-specific survival (DSS) in a univariate analysis. In a multivariate analysis, intratumoral and intrastromal CD103+ lymphocytes and pathological T and N factors were independent prognostic factors of the DSS. Significant concordance was found between the PD-L1 expression of primary tumors and metastatic lymph nodes as well as among tumor-infiltrating lymphocytes, CD8+ lymphocytes and CD103+ lymphocytes. Infiltration of CD103+ lymphocytes into the tumor was significantly correlated with an increased PD-L1 expression of cancer cells in both primary tumors and reginal lymph node metastases. Both the intratumoral infiltration of CD103+ lymphocytes and PD-L1 expression of cancer cells were significantly higher in lymph node metastases than in primary tumors. CONCLUSIONS: CD103+ lymphocyte infiltration in the primary tumor was shown to be strongly involved in the prognosis.

Relationship between Kita-Kyushu Lung Cancer antigen-1 expression and prognosis of cases with lung squamous cell carcinoma.

BACKGROUND: Previously, we identified the highly immunogenic cancer testicular antigen named Kita-Kyushu Lung Cancer antigen-1 (KK-LC-1). In this study, we analyzed the effect of KK-LC-1 expression on the prognosis of patients with resected squamous cell lung cancer. METHODS: Fifty squamous cell lung cancer patients, who received complete resection, were enrolled in this study. The expressions of KK-LC-1, CD8, human leukocyte antigen (HLA) class I, and programmed cell death protein ligand-1 (PD-L1) were assessed via immunohistochemistry staining using the specimens obtained from the participants. The association between the expression of the abovementioned molecules and patient prognosis was investigated. RESULTS: KK-LC-1 expression was observed in 21 of 50 recruited cases (42%). However, no significant correlation was found between KK-LC-1 expression and patient prognosis. The prognosis was significantly better in lung cancer cases with KK-LC-1 expression in which CD8+ T cells infiltrated the tumor. Regardless of the HLA class I expression or the PD-L1 expression, the KK-LC-1 expression in squamous cell lung cancer could not be detected as a significant prognostic factor. Furthermore, considering the polarity of the cancer tissue as epithelium, staining of KK-LC-1 tended to be strong in the area corresponding to the basal side of the tumor tissue. The Ki-67 expression was frequently observed in cancer cells on the basal side, which was consistent with the KK-LC-1 expression in representative four cases with KK-LC-1-positive squamous cell lung cancer. CONCLUSIONS: Our results indicated that lung squamous cell cancer patients with KK-LC-1 expression and the tumor infiltrating CD8+ T cells might exhibit better prognosis. KK-LC-1 might be highly expressed in cancer cells with high proliferative capacity. Larger cohort analysis is still required for further elucidation and validation of the results of this study.

Intraoperative peritoneal lavage cytology offers prognostic significance for gastric cancer patients with curative resection.

Outcomes of patients with gastric cancer who exhibit positive peritoneal lavage cytology findings (CY+ ) vary by diagnostic methods because of quantitative and qualitative cancer cell diversity. This study sought to establish practical diagnostic criteria for performing curative resections, based on peritoneal lavage cytology findings in gastric cancer patients. We enrolled 1028 patients with gastric cancer who underwent R0/1 (n = 911) or R2 (n = 117) resections and analyzed relationships between cancer cell findings in peritoneal lavage fluid and clinicopathological factors in the R0/1 group. We found 68 patients with CY+ status. Receiver operating characteristic analyses and multivariate analyses showed that the presence of ≥1 signet ring cell, ≥5 cell clusters or ≥50 isolated cancer cells in peritoneal lavage fluid predicted poor prognoses in the 68 CY+ patients. High-risk CY+ group patients with at least one of the above predictors had the highest hazard ratio (HR = 3.28, P < 0.001). The remaining (low-risk) patients had a survival curve similar to that of patients with a normal cytology. The high-risk CY+ patients who underwent R1 resection had poor prognoses despite no macroscopic peritoneal metastasis (2% 5-year survival)-equivalent to that of patients who underwent R2 resection. The CY+ criteria defined in this study could help identify candidates for curative resection as an initial therapy for gastric cancer.

Fibrous stroma is associated with poorer prognosis in lung squamous cell carcinoma patients.

INTRODUCTION: Cancer tissue is composed of various stromal cells forming cancer-specific microenvironments. Peritumoral stroma is reportedly composed of activated fibroblasts that can influence the biological properties of tumor cells, mainly their local aggressiveness and their ability. The aim of this study was to examine whether the histological properties of peritumoral stroma are correlated with squamous cell carcinoma (SqCC) aggressiveness and clinical outcome. METHODS: A series of 220 pathological stage I lung SqCC were categorized into two types according to the histological properties of the peritumoral stroma, "fibrous stroma type" (n = 85), and "thin stroma type" (n = 135), and compared the prognostic significance. Furthermore, we compared the immunohistochemical properties of the SqCC cells surrounded by "fibrous stroma" with those of the SqCC cells surrounded by "thin stroma." RESULTS: The prognosis of the patients with fibrous stroma-type tumors was significantly poorer than that of the thin stroma type with regard to both recurrence-free survival (p = 0.005) and overall survival (p = 0.008). A multivariate analysis showed that the presence of a fibrous stroma was an independent prognostic factor (p = 0.030). Compared with the SqCC cells with a thin stroma, the SqCC cells with a fibrous stroma exhibited reduced expression of E-cadherin (55.9 versus 126.0, p < 0.001) and an increased expression of laminin-5γ2 (94.6 versus 25.0, p = 0.001), matrix metalloproteinase-7 (26.0 versus 3.50, p = 0.009), and c-Met (64.0 versus 36.5, p = 0.033). CONCLUSION: SqCC with a fibrous stroma displayed higher invasive phenotype and were associated with a significantly poor prognosis. The current results suggest that the microenvironment created by both SqCC cells and the peritumoral fibroblasts may facilitate cancer aggressiveness.