Both the innate and adaptive immune systems contribute to tumor immunosurveillance in mice and humans; however, there is a paucity of direct evidence of a role for natural killer (NK) cells in this important process. In this study, we investigated the intratumoral phenotypic profile and functions of NK cells in primary human tumor specimens of non-small cell lung carcinoma (NSCLC). We used in situ methods to quantify and localize NK cells using the NKp46 marker and we characterized their phenotype in blood, tumoral, and nontumoral samples of NSCLC patients. Intratumoral NK cells displayed a profound and coordinated alteration of their phenotype, with a drastic reduction of NK cell receptor expression specifically detected in the tumoral region. According to their altered phenotype, intratumoral NK cells exhibited profound defects in the ability to activate degranulation and IFN-g production. We found that the presence of NK cells did not impact the clinical outcome of patients with NSCLC. Finally, we showed that tumor cells heterogeneously express ligands for both activating and inhibitory NK receptors. Taken together, our results suggest that the NSCLC tumor microenvironment locally impairs NK cells, rendering them less tumorcidal and thereby supportive to cancer progression. Cancer Res; 71(16); 5412-22. Ó2011 AACR.
Three hundred seven cases of patients who underwent operation for thymoma (196 of whom had myasthenia gravis) were analyzed to assess the prognostic values of Masaoka clinical staging, completeness of resection, histologic classification, history of myasthenia gravis, and postoperative radiotherapy. According to the Masaoka staging system, 135 thymomas were stage I, 70 were stage II, 83 were stage III, and 19 were stage IV. According to the Verley and Hollmann histologic classification system, 67 thymomas were type 1, 77 were type 2, 139 were type 3, and 24 were type 4. Two hundred sixty patients underwent complete resection, 30 underwent incomplete resection, and 17 underwent biopsy. Postoperative radiotherapy was performed mainly in cases of invasive or metastatic thymoma. Mean follow-up was 8 years; eight patients were unavailable for follow-up. The overall 10- and 15-year survivals were 67% and 57%, respectively. In univariate analysis, three prognostic factors were established: completeness of resection, Masaoka clinical staging, and histologic classification. Furthermore, among patients with stage III thymomas, survival was significantly higher for patients with complete resection than for patients with incomplete resection (p < 0.001). Completeness of resection should therefore be taken into account in clinical-pathologic staging. We did not find any significant difference with respect to disease-free survival between patients who had postoperative radiotherapy and those who did not. In multivariate analysis, the sole significant prognostic factor was completeness of resection. On the basis of these findings, a new clinical-pathologic staging system is proposed.
Purpose: If immune cells are involved in tumor surveillance and have a prognostic impact in most primary tumors, little is known about their significance in metastases. Because patients' survival is heterogeneous, even at metastatic stages, we hypothesized that immune cells may be involved in the control of metastases. We therefore characterized the tumor immune microenvironment and its prognostic value in colorectal and renal cell carcinoma (RCC) metastases, and compared it to primary tumors.Experimental Design: We analyzed by immunohistochemistry (n ¼ 192) and qPCR (n ¼ 32) the immune environments of colorectal carcinoma and RCC lung metastases.Results: Metastases from colorectal carcinoma and RCC have different immune infiltrates. Higher densities of DC-LAMP þ mature dendritic cells (P < 0.0001) and lower densities of NKp46 þ NK cells (P < 0.0001) were observed in colorectal carcinoma as compared to RCC metastases, whereas densities of T cells were similar. High densities of CD8 þ and DC-LAMP þ cells correlated with longer overall survival (OS) in colorectal carcinoma (P ¼ 0.008) and shorter OS in RCC (P < 0.0001). High NK-cell densities were associated with improved survival in RCC (P ¼ 0.002) but not in colorectal carcinoma. Densities of immune cells correlated significantly from primary to relapsing metastases for the same patient. A T H 1 orientation was found in colorectal carcinoma metastases, whereas a heterogeneous immune gene expression was found in RCC metastases.
Pneumonia acquired in-hospital represents a relatively frequent complication of lung resections, associated with an important percentage of postoperative morbidity and mortality.
Our experience shows that (1) CP and/or endometriosis-related pneumothoraces account for an important percentage of spontaneous pneumothoraces referred for surgery, (2) diaphragmatic abnormalities seem to play a fundamental role in their pathogenesis, and (3) management is difficult because of the high recurrence rate.
To determine long-term survival and prognostic factors, 208 patients with primary tracheal tumors were evaluated in a retrospective multicenter study including 26 centers. Ninety-four patients had squamous cell carcinoma, four had adenocarcinoma, 65 had adenoid cystic carcinoma, and 45 patients had miscellaneous tumors. The following resections were performed: tracheal resection with primary anastomosis, 165; carinal resection, 24; and laryngotracheal resection, 19. Postoperative mortality rate was 10.5% and correlated with the length of the resection, the need for a laryngeal release, the type of resection, and the histologic type of the cancer. Fifty-nine percent of patients with tracheal cancer and 43% of patients with adenoid cystic carcinomas had postoperative radiotherapy. The 5- and 10-year survivals, respectively, were 73% and 57% for adenoid cystic carcinomas and 47% and 36% for tracheal cancers (p < 0.05). Among patients with tracheal cancers, survival was significantly longer for those with complete resections than for those with incomplete resections. On the other hand, the presence of positive lymph nodes did not seem to decrease survival. Postoperative radiotherapy increased survival only in the case of incompletely resected tracheal cancers. Long-term prognosis was worsened by the occurrence of second primary malignancies in patients with tracheal cancers and by the occurrence of late pulmonary metastases in patients with adenoid cystic carcinomas.
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