This abstract was withdrawn by the authors. Citation Format: Huang C-S, Fann JC-Y, Chen H-H, Hsu G-C, Ho M-F, Chen S-C, Chen Y-J, Chen S-T, Chen C-Y, Sheen-Chen S-M, Chang H-T, Yeh D-C, Chao M, Yeh H-T, Cheng L, Chen D-R, Chang Y-C, Chang K-J. Withdrawn [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P6-02-13.
Immune checkpoint blockade (ICB) targeting PD-1/PD-L1 has been used for the treatment of head and neck squamous cell carcinoma (HNSCC). However, the overall response rate to ICB therapy for HNSCC remains less than 20%. It has recently been reported that the appearance of tertiary lymphoid structures (TLSs) in tumor tissue is correlated with better prognosis and response to ICB treatment. Here, we demonstrated an immune classification for the tumor microenvironment (TME) of HNSCC by analyzing The Cancer Genome Atlas (TCGA)–HNSCC data set and found that immunotype D with TLS enrichment had a better prognosis and response to ICB treatment. Furthermore, we observed that TLSs were present in a part of tumor samples of human papillomavirus (HPV) infection negative HNSCC (HPV− HNSCC) and were associated with the densities of dendritic cell (DC)–LAMP+ DCs, CD4+ T cells, CD8+ T cells, and progenitor T cells in TME. We established an HPV− HNSCC mouse model with TLS-enriched TME by overexpressing LIGHT in a mouse HNSCC cell line. We found that the induction of TLS formation enhanced the response to PD-1 blockade treatment in the HPV− HNSCC mouse model, accompanied by increases in DCs and progenitor exhausted CD8+ T cells in the TME. Elimination of CD20+ B cells attenuated the therapeutic effect of PD-1 pathway blockade in TLS+ HPV− HNSCC mouse models. These results indicate that TLSs contribute to the favorable prognosis and antitumor immunity of HPV− HNSCC. Inducing TLS formation in HPV− HNSCC tumors is a potential therapeutic method for improving the ICB response rate in patients with HPV− HNSCC.
Background: Endoscopic assisted nipple sparing mastectomy (E-NSM) alone or followed by immediate breast reconstruction (IBR) with implants or autologous flaps were reported to be associated with small inconspicuous incision and good cosmetic outcome. Robotic nipple sparing mastectomy (R-NSM), which introduce da Vinci surgical platform through a small axillary wound to perform NSM with (or without) IBR, was reported to have potential to overcome the technique difficulty of E-NSM and showed promising cosmetic outcome. However, few evidence was available compared the effectiveness and safety of R-NSM compared with E-NSM in the management of breast cancer. Methods: Patients with breast cancer received E-NSM or R-NSM performed from July 2010 to June 2018 were searched from breast surgery database at Changhua Christian Hospital (CCH), Taiwan. Data on clinicopathologic characteristics, type of surgery, complications and recurrence were analyzed to determine the effectiveness and oncologic safety of R-NSM and E-NSM. Patient-reported cosmetic outcome result was also obtained and compared. Results: A total of 127 E-NSM and 36 R-NSM procedures were found and data collected for analysis. About 77.8% of R-NSM group received breast reconstruction, and 78% of E-NSM group received breast reconstruction (P=0.982). The surgical margin involved rate was 2.8%(1/36) in R-NSM versus 3.4%(5/127) in E-NSM (P=1). The overall operation time was 281.5 ± 77.0 mins in R-NSM group versus 210.8 ± 55.5 mins in E-NSM group (P <0.001). Blood loss was mean 36.5 ± 33.7 ml in R-NSM group versus 88.0 ± 61.0 ml in E-NSM group (P <0.001). The hospital stay was 6.8 ± 1.3 days in R-NSM group versus 5.1 ± 1.3 in E-NSM group (<0.001). -From learning curve analysis, about 15-17 cases needed to significantly decrease operation time in E-NSM group, and in R-NSM group around 10-12 cases needed. -About 50 E-NSM and 25 R-NSM patients received post-operative questionnaire survey for cosmetic outcome evaluation and acceptance of operations. Patient-reported outcome survey showed that the satisfaction rate of R-NSM 96.4% group versus 94.8 in E-NSM group (p=0.96). The will to receive the same operation again if they could chose again: 100% in E-NSM group versus 96.4% in R-NSM group. -Cost analysis- The breast cancer operation cost was reimbursed by national insurance in Taiwan. The additional cost of E-NSM and IBR with Gel implant was 4,000-6,000 USD (according to different type of implants used). The cost of R-NSM and IBR with Gel implant was 10,000-12,000 USD (according to different type of implants used). The cost difference was about 2,500-3,300 USD higher in R-NSM group than in E-NSM group. Conclusion: Both E-NSM and R-NSM were equally effectively in the management of breast cancer with no different surgical margin involved rate, however, longer follow-up remained mandatory for oncologic safety evaluation. Shorter learning curve indicated more friendly operation plateform of robotic surgery in performing NSM. Relative longer operation time, and higher cost of R-NSM compared with E-NSM was observed. Longer hospitalization is biased from personal insurance consideration due to higher cost of R-NSM. Citation Format: Lai H-W, Chen S-T, Chen D-R, Kuo S-J. Comparison of robotic nipple sparing mastectomy (R-NSM) to endoscopic assisted nipple sparing mastectomy (E-NSM) in the management of breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-14-16.
Introduction Urokinase receptor (uPAR, CD87), a glycosylphosphatidylinositol-anchored protein, is considered to play an important role in inflammation and fibrinolysis. The Gram-negative bacterium Burkholderia pseudomallei is able to survive and replicate within leukocytes and causes melioidosis, an important cause of pneumonia-derived community-acquired sepsis in Southeast Asia. We here investigated the expression and function of uPAR both in patients with septic melioidosis and in a murine model of experimental melioidosis. Methods Using a translational approach we conducted a patient study in patients with culture-confirmed sepsis caused by B. pseudomallei, in vitro experiments using wild-type (WT) and uPAR knockout (KO) cells, and mouse studies using WT and uPAR KO mice inoculated with B. pseudomallei. Results uPAR mRNA and surface expression was increased in patients with septic melioidosis in/on both peripheral blood monocytes and granulocytes as well as in the pulmonary compartment during experimental pneumonia-derived melioidosis in mice. uPAR-deficient mice intranasally infected with B. pseudomallei showed an enhanced growth and dissemination of B. pseudomallei when compared with WT mice, corresponding with increased pulmonary and hepatic inflammation. uPAR KO mice demonstrated significantly reduced neutrophil migration towards the pulmonary compartment after inoculation with B. pseudomallei. Further in vitro experiments showed that uPARdeficient macrophages and granulocytes display a markedly impaired phagocytosis of B. pseudomallei. Additional studies showed that uPAR deficiency did not influence hemostatic and fibrinolytic responses during severe melioidosis. Conclusions These data suggest that uPAR is crucially involved in the host defense against sepsis caused by B. pseudomallei by facilitating the migration of neutrophils towards the primary site of infection and subsequently facilitating the phagocytosis of B. pseudomallei. P2 A comparison of acute lung inflammation in Klebsiella pneumoniae B5055-induced pneumonia and sepsis in BALB/c mice
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