Ninety percent of the adverse outcomes occur in 10% of patients: can we identify the populations at high risk of developing peritoneal metastases after curative surgery for colorectal cancer?

BACKGROUND: Peritoneal metastases (PM) occur in 3.4-6.3% after curative surgery for non-metastatic colorectal cancer. Systematic "2nd look" surgery helps overcoming the diagnostic problem but can be only proposed to selected patients. The aim of this study was to update the knowledge on risk factors of developing PM after curative surgery for colorectal cancer. METHODS: A systematic review of the literature published between 2011 and 2016 was made, searching for all clinical studies reporting the incidence of recurrent PM after curative surgery for colorectal cancer and factors associated with the primary tumour that were likely to influence this recurrence rate. RESULTS: Seven new clinical studies were considered informative for risk factors and added to the 16 reviewed in 2013. Even if the level of evidence was low, data suggested rates of recurrent PM at 1 year between 54% and 71% after completely resected synchronous PM, between 62% and 71% after resection of isolated synchronous ovarian metastases, of 27% after surgery for a perforated primary tumour, of 16% after surgery for a pT4 tumour, and between 11% and 36% after surgery for a mucinous histological subtype. No new risk factor was identified. CONCLUSIONS: Evidence regarding the incidence of recurrent PM after curative surgery for colorectal cancer is poor. Situations at higher risk of recurrent PM are synchronous PM, synchronous isolated ovarian metastases, perforated primary tumour with serosa invasion and mucinous histological subtype.

Identification of a novel PD-L1 positive solid tumor transplantable in HLA-A*0201/DRB1*0101 transgenic mice.

HLA-A*0201/DRB1*0101 transgenic mice (A2/DR1 mice) have been developed to study the immunogenicity of tumor antigen-derived T cell epitopes. To extend the use and application of this mouse model in the field of antitumor immunotherapy, we described a tumor cell line generated from a naturally occurring tumor in A2/DR1 mouse named SARC-L1. Histological and genes signature analysis supported the sarcoma origin of this cell line. While SARC-L1 tumor cells lack HLA-DRB1*0101 expression, a very low expression of HLA-A*0201 molecules was found on these cells. Furthermore they also weakly but constitutively expressed the programmed death-ligand 1 (PD-L1). Interestingly both HLA-A*0201 and PD-L1 expressions can be increased on SARC-L1 after IFN-γ exposure in vitro. We also obtained two genetically modified cell lines highly expressing either HLA-A*0201 or both HLA-A*0201/ HLA-DRB1*0101 molecules referred as SARC-A2 and SARC-A2DR1 respectively. All the SARC-L1-derived cell lines induced aggressive subcutaneous tumors in A2DR1 mice in vivo. The analysis of SARC-L1 tumor microenvironment revealed a strong infiltration by T cells expressing inhibitory receptors such as PD-1 and TIM-3. Finally, we found that SARC-L1 is sensitive to several drugs commonly used to treat sarcoma and also susceptible to anti-PD-L1 monoclonal antibody therapy in vivo. Collectively, we described a novel syngeneic tumor model A2/DR1 mice that could be used as preclinical tool for the evaluation of antitumor immunotherapies.