Accumulating preclinical evidence suggests that anticancer immune responses contribute to the success of chemotherapy. The predictive significance of tumor-infiltrating lymphocytes (TILs) for response to neoadjuvant chemotherapy in non-small cell lung cancer (NSCLC) remains unknown. The aim of this study was to investigate the prognostic and predictive value of TIL subtypes in patients with advanced NSCLC treated with platinum-based chemotherapy. In total, 159 patients with stage III and IV NSCLC were retrospectively enrolled. The prevalence of CD3(+), CD4(+), CD8(+) and Foxp3(+) TILs was assessed by immunohistochemistry in tumor tissue obtained before chemotherapy. The density of TILs subgroups was treated as dichotomous variables using the median values as cutoff. Survival curves were estimated by the Kaplan-Meier method, and differences in overall survival between groups were determined using the Log-rank test. Prognostic effects of TIL subsets density were evaluated by Cox regression analysis. The presence of CD3(+), CD4(+), CD8(+), and FOXP3(+) TILs was not correlated with any clinicopathological features. Neither the prevalence of TILs nor combined analysis displayed obvious prognostic performances for overall survival in Cox regression model. Instead, higher FOXP3(+)/CD8(+) ratio in tumor sites was an independent factor for poor response to platinum-based chemotherapy in overall cohort. These findings suggest that immunological CD8(+) and FOXP3(+)Tregs cell infiltrate within tumor environment is predictive of response to platinum-based neoadjuvant chemotherapy in advanced NSCLC patients. The understanding of the clinical relevance of the microenvironmental immunological milieu might provide an important clue for the design of novel strategies in cancer immunotherapy.

This trial is registered at ClinicalTrials.gov: ID NCT01697410.

Background: Although community-acquired Staphylococcus aureus pneumonia with highly virulent Panton-Valentine leukocidin (PVL)-positive strains, a severe disease with significant lethality, is rare, especially in adult and adolescent patients, recent reports highlight that these infections are on the rise. Objectives: To describe the demographic and clinical features of reported cases of life-threatening community-acquired S. aureus pneumonia with usually PVL-positive strains in adult and adolescent patients, to evaluate the variables related to death, and to select a more appropriate antimicrobial treatment for this potentially deadly disease. Methods: We summarized all of the 92 reported cases and our case. The effect of 5 variables on mortality was measured using logistic regression. Results:S. aureus community-acquired pneumonia (CAP) with usually PVL-positive strains is a severe disease with significant lethality, i.e. 42.9%; a short duration of the time from the onset of symptoms to death, i.e. 5.5 ± 10.1 days, and prolonged hospital admissions, i.e. 33.2 ± 29.5 days. Seventy-three cases have been tested for the gene for PVL, and 71 strains have been found to carry the PVL gene. Logistic regression analysis showed that leucopenia (p = 0.002), influenza-like symptoms or laboratory-confirmed influenza (p = 0.011), and hemoptysis (p = 0.024) were the factors associated with death. Antibiotic therapies inhibiting toxin production were associated with an improved outcome in these cases (p = 0.007). Conclusions: Physicians should pay special attention to those patients who acquired severe CAP during influenza season and have flu-like symptoms, hemoptysis, and leucopenia, and they should consider S. aureus more frequently among the possible pathogens of severe CAP. Empiric therapy for severe CAP with this distinct clinical picture should include coverage for S. aureus. Targeted treatment with antimicrobials inhibiting toxin production appears to be a more appropriate selection.

Fundamental studies have suggested that matrix metalloproteinases-7 (MMP-7) expression is associated with chemoresistance and constitutes a prognostic factor in several solid tumors. The present study assessed the prognostic and predictive value of MMP-7 in tumors of patients with advanced non-small cell lung cancer (NSCLC) treated with platinum-based chemotherapy. In total, 159 patients with stage III and IV NSCLC were retrospectively enrolled. Immunohistochemistry was performed to evaluate the expression of MMP-7, apoptosis-related proteins Bcl-2, Bax, Fas and FasL and the Ki-67 proliferation marker. The TUNEL (terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling) method was performed to investigate tumor apoptosis. Ninety carcinomas (56.6%) were identified as high expression of MMP-7. Overexpression of MMP-7 was more frequent in adenocarcinomas than in squamous cell carcinomas (P = 0.032). The expression of MMP-7 was positively related with Ki-67 index and Bcl-2, but not apoptosis index. MMP-7 status was correlated inversely with response to chemotherapy in overall patients (response rates, 20.0% and 35.8%, for patients with high-MMP-7 and low-MMP-7 tumors, respectively, P = 0.036), especially in adenocarcinoma (P = 0.021), but not in patients with squamous cell carcinomas (P = 0.373). The overall survival was significantly lower in NSCLC patients with high MMP-7 than in those with low MMP-7 (P < 0.001). A Cox regression analyses also demonstrated MMP-7 status to be a significant prognostic factor (hazard ratio, 5.49; P = 0.001). These findings suggest that the expression level of MMP-7 in tumor cells is predictive of response to chemotherapy and outcome in patients with advanced NSCLC receiving platinum-based chemotherapy. (Cancer Sci 2008; 99: 2185-2192) L ung cancer is the leading cause of cancer-related death in the world and non-small cell lung cancers (NSCLC) comprise more than 75% of all lung cancers. About 70% of NSCLC cases are advanced at diagnosis and treated with chemotherapy and radiotherapy. Platinum-based combinations with newer agents have been widely accepted as first-line options in the treatment of advanced NSCLC, but the frequent development of platinumresistance is a major obstacle at present.(1) A large effort has been devoted and the precise mechanisms remain unclear. Therefore, identification and implementation of markers predictive of response appear to be one way to select sensitive regimen based on the biological characteristics of the tumors.Increasing evidence indicates that local microenvironment of the tumor plays an important role in the development of chemoresistance.(2) Matrix metalloproteinases (MMP) maintain the proper homeostasis of extracellular matrix (ECM) and stabilize cell-matrix interaction. (3,4) As the smallest (28 kDa) member of the MMP family, MMP-7 (matrilysin) has been related to tumor invasion and metastasis.(5) More recently, fundamental data implicated the role of MMP-7 in the development of chemoresistance. Vargo-Gogola...

Clin Invest Med 2009; 32 (1): E70-E77. AbstractPurpose: To clarify the clinical features and imaging characteristics of non-AIDS patients with pulmonary cryptococcosis. Methods: We retrospectively collected 15 HIV-negative patients with pathology-proved pulmonary cryptococcosis from Sep1992 to Jan 2008. Their medical records and radiological data were reviewed and analyzed. Results: Only one patient was asymptomatic.Thirteen patients were immunocompetent and two were immunosuppressed. Three patients had associated cryptococcosis meningitis. The most common radiographic abnormalities were multiple pulmonary nodules or masses, seen in 8 and 5 cases of patients respectively. 14 patients received specific therapy for Cryptococcus neoformans. Two patients died. In the 11 patients with isolated pulmonary cryptococcosis, treatment consisted of fluconazole alone (n=7), in combination with amphotericin B (n=2), and both 5flucytosine and amphotericin B (n=2). For the other 2 patients with cryptococcosis meningitis, one was treated with amphotericin B alone and the other with fluconazole combined with amphotericin B and 5-flucytosine. Conclusions: Non-AIDS patients might also susceptible to cryptococcosis infection. Histological examination is the principal method of diagnosis. The most common CT findings are solitary or multiple nodules with or without cavitation in the subpleural areas of the lung.