SUMMARYThe immunological privilege of the anterior chamber (AC) of the eye is due, at least in part, to a selective antigen-specific down-regulation of delayed-type hypersensitivity (DTH) and a normal induction of antibody responses: a phenomenon that has been termed anterior chamber-associated immune deviation (ACAID). This dichotomy in the systemic immune responses is suggestive of a Thelper type-2 (Th2)-dominated immune phenotype in which a Th2 cell population is preferentially activated and cross-regulates T-helper type-1 (Th1) effector elements. This hypothesis was tested by comparing the cytokine pattern of antigen-pulsed spleen cells from mice primed in the anterior chamber with antigens that induce ACAID with responses in hosts primed with antigens that do not induce ACAID. The results indicated that CD4 spleen cells from hosts primed in the AC with antigens that induce ACAID produced significant quantities of interleukin-10 (IL-10) but insignificant levels of IL-2, IL-4 and interferon-g (IFN-g). In contrast, hosts primed in the AC with antigens that do not induce ACAID, but instead elicit normal DTH, displayed cytokine patterns indicative of a Th1 response: significant quantities of IL-2 and IFN-g were produced while IL-4 and IL-10 secretion was insignificantly different from normal controls. The immunological phenotype of the AC-primed hosts could be altered by systemic treatment with antibodies against either a Th1 cytokine (IFN-g) or a Th2 cytokine (IL-10). Hosts treated with anti-IL-10 antibody and subsequently primed in the AC with ACAID-inducing antigens developed normal DTH responses, while hosts treated with anti-IFN-g antibody and primed in the AC with antigens that normally produce positive DTH responses failed to develop positive DTH. Collectively the results support the proposition that immune privilege in the AC of the eye is due to the selective activation of a Th2 population that cross-regulates Th1 responses.

Prostate cancer is a common malignancy driven by the androgen receptor (AR) pathway, with androgen deprivation therapy (ADT) being a standard treatment. However, the development of castration-resistant prostate cancer (CRPC) poses a significant challenge. CRPC is characterized by significantly increased tumor heterogeneity and lineage plasticity. Current research has primarily emphasized intrinsic tumor mechanisms, paying less attention to the role of the tumor microenvironment in cancer recurrence and drug resistance. In their recent study published in Cancer Cell, Wang and colleagues employed single-cell RNA sequencing in genetically engineered mouse models (GEMMs) with prostate tumors at different stages. They revealed that SPP1+ myofibroblastic cancer-associated fibroblasts (myCAFs), induced by ADT, play an instrumental role in CRPC development. Their work also underscores the association between therapy-induced phenotypic alterations of cancer-associated fibroblasts (CAFs) and disease progression. This discovery highlights the potential for stromal compartment targeting as a means to mitigate CRPC development and overcome treatment resistance.