Anti-IFNGR1 monoclonal antibody, clone CC2F3 [FITC]

IFN-gamma plays an important role in innate and adaptive immunity. IFN-gamma signaling is also involved in tumorigenesis, with both pro- and antitumor activities documented. We here report the characterization of intestinal tumorigenesis in Apc(Min/+) mice that lack IFN-gamma receptor. We observed that Ifngr1(-/-)Apc(Min/+) mice are shorter-lived than Ifngr(1+/+)Apc(Min/+) mice. The tumors in Ifngr(1-/-)Apc(Min/+) mice are more likely to progress into invasive adenocarcinomas. Gene expression profiling by RNA sequencing revealed a significant upregulation of genes involved in inflammation and tissue remodeling in tumors of Ifngr1(-/-)Apc(Min/+) mice when compared to those in Ifngr1(+/+)Apc(Min/+) mice. In particular, five genes encoding matrix metallopeptidases (MMPs) were among the upregulated. On the other hand, genes that promote or maintain intestinal differentiation, such as Cdx2, Cdhr2 and Cdhr5, were downregulated. Tumorassociated macrophages were more abundant and were more favored toward M2 polarization in Ifngr1(-/-)Apc(Min/+) mice than in Ifngr1(+/+)Apc(Min/+) mice. Furthermore, the Ifngr1 was significantly downregulated in intestinal tumors when compared to mucosa. A similar trend was noted for human colorectal carcinomas. Together, our results indicate that adequate IFN-gamma signaling is critical for maintaining a tumor-prohibitive microenvironment.

Longitudinal studies in Sudan show ethnic differences in incidence and clinical phenotypes associated with Leishmania donovani. Immunologically, bias in type 1 vs type 2 cytokine responses is important To determine whether polymorphisms at IL4/IL9 or IFNGR1 contribute to susceptibility, we examined 59 multicase families of visceral leishmaniasis (VL) with/without post Kala-azar dermal leishmaniasis (PKDL). Multipoint nonparametric analysis (Allegro) linked IL4/IL9 to VL per se (P= 0.002). Transmission disequilibrium testing with robust variance estimates confirmed association in the presence of linkage between VL per se and IL4 (P= 0.008) but not IL9. Stepwise logistic regression analysis showed both IL4RP2 and IL4RP1 markers contributed significantly to the association, suggesting a common disease-associated haplotype. In contrast, IFNGR1 was linked (P= 0.031) and associated (P= 0.007) to PKDL but not VL or VL per se. Hence, polymorphism in a type 2 cytokine gene influences underlying susceptibility to VL, whereas IFNGR1 is specifically related to susceptibility to PKDL.