Anti-CD45 monoclonal antibody, clone KT-94 [FITC]

IMPORTANCE Marine omega-3 polyunsaturated fatty acids (PUFAs), including eicosapentaenoic acid, docosahexaenoic acid, and docosapentaenoic acid, possess potent immunomodulatory activity and may protect against cancer development. However, evidence relating marine.-3 PUFAs to colorectal cancer (CRC) risk remains inconclusive. OBJECTIVE To test the hypothesis that marine omega-3 PUFA intakemay be associated with lower risk of CRC subsets characterized by immune infiltrate. DESIGN, SETTING, AND PARTICIPANTS This prospective cohort studywas conducted among participants in the Nurses' Health Study (1984-2010) and Health Professionals Follow-up Study (1986-2010). EXPOSURES Intake of marine omega-3 PUFAs. MAIN OUTCOMES AND MEASURES Incidence of CRC characterized by CD3(+), CD8(+), CD45RO (PTPRC)(+), or FOXP3(+) T-cell densities in tumor tissue, measured by immunohistochemical and computer-assisted image analysis. RESULTS Among 173 229 predominantly white participants, 125 172 with 2 895 704 person-years of follow-up provided data about marine omega-3 PUFA intake every 4 years through a validated food frequency questionnaire and followed up for incident CRC evaluation. Of 2504 CRC cases, we documented 614 (252 men, 362 women) from which we could assess T-cell infiltration in the tumor microenvironment. The inverse association of marine omega-3 PUFAs intake with CRC risk differed according to FOXP3(+) T-cell infiltration: compared with intake of less than 0.15 g/d of marine omega-3 PUFAs, intake of at least 0.35 g/d was associated with a multivariable hazard ratio (HR) of 0.57 (95% CI, 0.40-0.81; P <.001 for trend) for FOXP3(+) T-cell-high tumors. In contrast, the HR for FOXP3(+) T-cell-low tumors was 1.14 (95% CI, 0.8-1.60) (P =.77 for trend; P =.01 for heterogeneity). No statistically significant differential association was found for high-density tumors (compared with low-density tumors) according to CD3(+), CD8(+), or CD45RO(+) cell density (P >=.34 for heterogeneity for all comparisons). In functional assays, the suppressive activity of regulatory T cells was approximately 2-fold lower (T-effector-cell proliferation, >= 64% vs 38%) when preincubated with docosahexaenoic acid at 50 mu M, 100 mu M, and 200 mu M concentrations than without docosahexaenoic acid (P <.001 for all comparisons). CONCLUSIONS AND RELEVANCE High marine omega-3 PUFA intake was associated with lower risk of CRC with high-level, but not low-level, FOXP3(+) T-cell density, suggesting a potential role of omega-3 PUFAs in cancer immunoprevention through modulation of regulatory T cells.

P>The uncommon C77G polymorphism of the Protein-Tyrosine Phosphatase (PTPRC) gene (PTPRC; previously termed CD45) could confer an increased risk of immunopathology. This study compared the outcome of children following human leucocyte antigen-matched unrelated haematopoietic-stem cell transplantations (HSCT) from donors carrying (C77G cases: n = 8) or not (controls: n = 36) the PTPRC C77G polymorphism. Transmission of the PTPRC C77G polymorphism through the graft was suggested by unusual CD45RA phenotype in the donors and/or in the recipients after, but not before HSCT. Restriction-Fragment Length Polymorphism and sequencing confirmed the polymorphism. Overall survival rates were similar in C77G cases and controls (63% vs. 61%). Acute leukaemia relapse tended to be less frequent in C77G cases (0% vs. 32%; P = 0 center dot 09). Among recipients surviving >= 30 d, acute GVHD (aGVHD) >= grade 2 tended to be more frequent (100% vs. 58%; P = 0 center dot 07) and the rate of steroid-refractory or -dependant aGVHD higher (67% vs. 28%) in C77G cases. Finally, extensive chronic GVHD tended to occur more frequently (40% vs. 9%) in C77G cases. Recovery of lymphocyte subsets and virus-specific CD4 was similar in C77G cases and controls while interleukin 2 (IL2)-responses through CD3 stimulation were higher in C77G cases (P = 0 center dot 004). In conclusion, HSCT from PTPRC C77G donors could increase GVHD risk without compromising overall survival. Altered IL2-responses could be involved in this process.