Aspirin use after the diagnosis of CRC is independently associated with improved CSS and OS.

Human CD4 ؉ FoxP3 ؉ T cells are functionally and phenotypically heterogeneous providing plasticity to immune activation and regulation. To better understand the functional dynamics within this subset, we first used a combined strategy of subcellular fractionation and proteomics to describe differences at the protein level between highly purified human CD4 ؉ CD25 ؉ and CD4 ؉ CD25 ؊ T-cell populations. This identified a set of membrane proteins highly expressed on the cell surface of human regulatory T cells

Objective High rates of systemic failure in locally advanced rectal cancer call for a rational use of conventional therapies to foster tumor-defeating immunity. Methods We analyzed the high-mobility group box-1 (HMGB1) protein, a measure of immunogenic cell death (ICD), in plasma sampled from 50 patients at the time of diagnosis and following 4 weeks of induction chemotherapy and 5 weeks of sequential chemoradiotherapy, both neoadjuvant modalities containing oxaliplatin. The patients had the residual tumor resected and were followed for long-term outcome. Results Patients who met the main study end point-freedom from distant recurrence-showed a significant rise in HMGB1 during the induction chemotherapy and consolidation over the chemoradiotherapy. The higher the ICD increase, the lower was the metastatic failure risk (hazard ratio 0.26, 95% confidence interval 0.11-0.62, P = 0.002). However, patients who received the full-planned oxaliplatin dose of the chemoradiotherapy regimen had poorer metastasis-free survival (P = 0.020) than those who had the oxaliplatin dose reduced to avert breach of the radiation delivery, which is critical to maintain efficient tumor cell kill and in the present case, probably also protected the ongoing radiation-dependent ICD response from systemic oxaliplatin toxicity. Conclusion The findings indicated that full-dose induction oxaliplatin followed by an adapted oxaliplatin dose that was compliant with full-intensity radiation caused induction and maintenance of ICD and as a result, durable disease-free outcome for a patient population prone to metastatic progression. Keywords Immunogenic cell death • Rectal cancer • Oxaliplatin • Radiotherapy • Metastasis Abbreviations CI Confidence interval CRC Colorectal cancer CRT Chemoradiotherapy DMFS Distant metastasis-free survival FLOX The Nordic FLOX regimen (oxaliplatin, fluorouracil, folinic acid)

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Background. We examined overall and disease-free survivals in a cohort of patients subjected to resection of liver metastasis from colorectal cancer (CRLM) in a 10-year period when new treatment strategies were implemented. Methods. Data from 239 consecutive patients selected for liver resection of CRLM during the period from 2002 to 2011 at a single center were used to estimate overall and disease-free survival. The results were assessed against new treatment strategies and established risk factors. Results. The 5-year cumulative overall and disease-free survivals were 46 and 24%. The overall survival was the same after reresection, independently of the number of prior resections and irrespectively of the location of the recurrent disease. The time intervals between each recurrence were similar (11 ± 1 months). Patients with high tumor load given neoadjuvant chemotherapy had comparable survival to those with less extensive disease without neoadjuvant chemotherapy. Positive resection margin or resectable extrahepatic disease did not affect overall survival. Conclusion. Our data support that one still, and perhaps to an even greater extent, should seek an aggressive therapeutic strategy to achieve resectable status for recurrent hepatic and extrahepatic metastases. The data should be viewed in the context of recent advances in the understanding of cancer biology and the metastatic process.

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Objective: The main objective of the present study was to explore contact-independent immune suppressive mechanisms by humoral factors in malignant ascites from ovarian carcinoma that target effector T cells. Methods: Flow cytometry was the main method used to detect T cell function as assessed by CFSE-proliferation rate, in the presence of different concentrations of ascites fluid. Cell-free ascites was sometimes pretreated using a biochemical approach. Different antibody inhibitors were used to reverse the ascites-induced inhibition of T cell proliferation. Results: By culturing T cells in cell-free ascites we demonstrated malignant ascites fluid to be highly immunosuppressive both against autologous and allogeneic T cells (n=6, p<0,001). The inhibitory factor(s) in ascites did not appear to be secreted from the ovarian carcinoma (OC) cells, as transfer of culture media from tumor cells isolated from OC patients or the ovarian cancer cell-line SKOV-3 did not suppress effector T cell functions in vitro. A more detailed characterization demonstrated that the inhibition could not be reversed by targeting potential suppressive mechanisms like IL-6, IL-8, IL-10, CTLA-4, PD-1, B7-DC, B7-H1 or PI3K (n=5). Furthermore, we found the inhibitory factor(s) to be sensitive to proteases and denatured by heat and acetone (n=3). Conclusion: In conclusion, our data indicate the presence of a yet unknown inhibitory protein factor(s) in malignant cell-free ascites, not secreted by tumor cells, but possibly by immune cells such as regulatory T cells (Tregs).

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