Carcinomas assemble a filamentous CXCL12-keratin-19 coating that suppresses T cell-mediated immune attack.

Cancer immunotherapy frequently fails because most carcinomas have few T cells, suggesting that cancers can suppress T cell infiltration. Here, we show that cancer cells of human pancreatic ductal adenocarcinoma (PDA), colorectal cancer, and breast cancer are coated with transglutaminase-2 (TGM2)-dependent covalent CXCL12-keratin-19 (KRT19) heterodimers that are organized as filamentous networks. Since a dimeric form of CXCL12 suppresses the motility of human T cells, we determined whether this polymeric CXCL12-KRT19 coating mediated T cell exclusion. Mouse tumors containing control PDA cells exhibited the CXCL12-KRT19 coating, excluded T cells, and did not respond to treatment with anti-PD-1 antibody. Tumors containing PDA cells not expressing either KRT19 or TGM2 lacked the CXCL12-KRT19 coating, were infiltrated with activated CD8+ T cells, and growth was suppressed with anti-PD-1 antibody treatment. Thus, carcinomas assemble a CXCL12-KRT19 coating to evade cancer immune attack.

Laparoscopic Hartmann's procedure: a viable option for treatment of acutely perforated diverticultis.

BACKGROUND: A laparoscopic technique for acutely perforated diverticulitis (i.e., laparoscopic Hartmann's procedure) has not been described. The authors present their technique for laparoscopic sigmoid resection, end colostomy, and subsequent laparoscopic takedown of colostomy. METHODS: A retrospective review of patients with Hinchey III/IV diverticulitis who underwent a laparoscopic Hartmann's procedure was performed in this study. Laparoscopic takedown of sigmoid colostomy was performed 2 to 3 months later. Data from these procedures including estimated blood loss (EBL), length of the operative procedure, patient outcomes, and demographics were evaluated. RESULTS: Seven patients with a mean age of 49.7 years underwent laparoscopic sigmoid colectomy with end colostomy. None of these patients had a history of diverticulitis. Their mean EBL was 138 ml, and their mean operative time was 154 min. None of the procedures required conversion to use of a hand port or conversion to open procedure. The average time to return of bowel function was 3.7 days, with one patient experiencing a postoperative ileus. The mean postoperative hospital stay was 6.6 days. There were no complications. Laparoscopic Hartmann's takedown was performed for all the patients approximately 2 to 3 months later. The mean EBL was 107 ml, and the average operative time was 189 min. One patient had intraoperative anastomotic leak, which was successfully repaired and retested. Again, none of the procedures required the use of a hand port or a laparotomy. The average time to return of bowel function was 3.4 days. The average length of hospital stay was 5.3 days, with one patient experiencing a fat necrosis. CONCLUSIONS: Laparoscopic Hartmann's procedure and laparoscopic takedown are technically feasible procedures with reasonable outcomes.