Prognostic value of tumor-infiltrating lymphocytes differs depending on histological type and smoking habit in completely resected non-small-cell lung cancer.

BACKGROUND: T-cell infiltration in tumors has been used as a prognostic tool in non-small-cell lung cancer (NSCLC). However, the influence of smoking habit and histological type on tumor-infiltrating lymphocytes (TILs) in NSCLC remains unclear. PATIENTS AND METHODS: We evaluated the prognostic significance of TILs (CD4+, CD8+, CD20+, and FOXP3+) according to histological type and smoking habit using automatic immunohistochemical staining and cell counting in 218 patients with NSCLC. RESULTS: In multivariate survival analyses of clinical, pathological, and immunological factors, a high ratio of FOXP3+ to CD4+ T cells (FOXP3/CD4) [hazard ratio (HR): 4.46, P < 0.01 for overall survival (OS); HR: 1.96, P < 0.05 for recurrence-free survival (RFS)] and a low accumulation of CD20+ B cells (HR: 2.45, P = 0.09 for OS; HR: 2.86, P < 0.01 for RFS) were identified as worse prognostic factors in patients with adenocarcinoma (AD). In non-AD, a low number of CD8+ T cells were correlated with an unfavorable outcome (HR: 7.69, P < 0.01 for OS; HR: 3.57, P < 0.02 for RFS). Regarding smoking habit in AD, a high FOXP3/CD4 ratio was poorly prognostic with a smoking history (HR: 5.21, P < 0.01 for OS; HR: 2.38, P < 0.03 for RFS), whereas a low accumulation of CD20+ B cells (HR: 4.54, P = 0.03 for OS; HR: 2.94, P < 0.01 for RFS) was confirmed as an unfavorable factor in non-smokers with AD. CONCLUSIONS: A low number of CD8+ T cells in non-AD, a high FOXP3/CD4 ratio in smokers with AD, and a low number of CD20+ B cells in non-smokers with AD were identified as independent unfavorable prognostic factors in resected NSCLC. Evaluating the influence of histological type and smoking habit on the immunological environment may lead to the establishment of immunological diagnosis and appropriate individualized immunotherapy for NSCLC.

A bioactive glass powder-ammonium hydrogen phosphate composite for repairing bone defects.

Bioactive glass powder (AW-G) was made into a rigid compound by mixing with ammonium hydrogen phosphate and was evaluated as a bone-defect filler. The proximal metaphysis of the rat tibia was drilled and packed with (a) polymethyl-methacrylate (PMMA) bone cement, (b) AW-G powder, (c) AW-G powder with ammonium hydrogen phosphate (AW-G)-(A-P), or (d) nothing, as a control. The animals, with different implantation periods up to 24 weeks, were sacrificed and the defective sites were histologically analyzed. The results revealed direct bonding between the bone tissue and the (AW-G)-(A-P). The general inflammatory reaction of (AW-G)-(A-P) was less than that of PMMA bone cement. The compressive strength of (AW-G)-(A-P) implanted subcutaneously into rats was measured chronologically and deterioration did not occur during a period of 24 weeks. The rigidity increased to 1.6 times 6 months after implantation as compared with the initial value. This compound can be used as paste and is transformed into a rigid compound in about 4 min without noticeable elevation of the temperature. Thus, this (AW-G)-(A-P) composite can be used as a bone defect filler, and there is a possibility that it can even be used as a bone cement if higher rigidity can be attained.