Biology subjects

Armas Cayarga, A.

Publications and source records attributed to Armas Cayarga, A..

2 recordsLinked to original sources

bioRxiv2026

Trans-presentation of IL-15 by IL15Rα attenuates tumor immune surveillance and is dispensable for IL-15-dependent tumor growth control

BackgroundIL-15 is a promising cytokine for cancer immunotherapy. IL-15 promotes differentiation and homeostasis of innate and adaptive immune cells, and their cytolytic effector functions. IL-15 receptor is composed of IL-15R, IL-15R{beta} and the common {gamma}c chains. IL-15 is also trans-presented as IL-15R:IL-15 complex to IL-15R{beta}:{gamma}c on neighboring cells. IL-15R is dispensable for early immune response to infections and in autoimmune diabetes. The role of IL-15R in antitumor immune responses remains unclear. MethodsIn WT, Il15-/- and Il15ra-/- mice, we studied the growth of syngeneic tumor cell lines and tumor immune surveillance against endogenous fibrosarcoma induced by methylcholanthrene (MCA). Immune gene signature and total proteome analysis were performed on MCA-induced tumors. ResultsLack of IL-15 or IL-15R did not enhance the growth of implanted tumor cell lines, despite reduced immune cell infiltration. MCA-induced tumor incidence was reduced in mice lacking IL-15R but not IL-15, although both are required for efficient tumor immunoediting. Il15-/- and Il15ra-/- tumors showed reduced Ifng expression but displayed differential modulation of Ifng-responsive genes. Proteome profiles of Il15-/- tumors, but not tumor-derived cell lines, showed significant reduction of antigen presentation pathways. B16-F10 melanoma cells expressing NLRC5, the IFN{gamma}-induced transcriptional activator of tumor antigen presentation, still required IL-15 but not IL-15R for efficient tumor control. ConclusionsOur findings show that IL-15 plays a negligible role in immunosurveillance against spontaneous tumor development, whereas IL-15R restrains immunosurveillance. Neither IL-15 nor IL-15R have a significant impact on implanted tumor models, although IL-15 facilitates efficient control of highly immunogenic tumors for which IL-15R is dispensable.

immunology↗

bioRxiv2026

SOCS1 expression in prostate epithelial cells is essential for tissue homeostasis and tumor suppression

Suppressor of cytokine signaling 1 (SOCS1) negative regulates inflammatory cytokine production and attenuates oncogenic growth factor signaling pathways. Reduced SOCS1 protein expression in human prostate cancer correlates with greater disease severity. To define the physiological functions of SOCS1 functions in the prostate, we conditionally ablated Socs1 in prostate epithelial cells of C57BL/6 mice. These Socs1{Delta}PE mice exhibited normal prostate development, maturation and lobular architecture. However, adult Socs1{Delta}PEmice developed progressive epithelial hyperplasia and inflammatory cell infiltration that were temporally and spatially distinct. SOCS1-deficient prostate showed increased epithelial cell proliferation and elevated oxidative stress markers, and prostate organoids recapitulated this hyperplasia phenotype. Diet-induced obesity exacerbated both hyperplasia and inflammation in SOCS1-deficient prostate. Upon transurethral infection with uropathogenic Escherichia coli UPEC1677 expressing the genotoxin colibactin, Socs1{Delta}PE mice developed invasive prostate cancer with complete loss of lobular architecture, whereas control mice developed hyperplasia and pre-neoplastic lesions. In vitro, SOCS1-deficient prostate organoid-derived epithelial cells exhibited increased DNA damage following exposure to UPEC1677. Deletion of the colibactin biosynthetic gene clbP in UPEC1677 abolished its ability to induce DNA damage in SOCS1-deficient cells and to drive prostate cancer in vivo. Proteomic analysis of prostate organoids revealed dysregulation of basal and luminal epithelial lineage markers and signaling pathway proteins that could promote neoplasia in SOCS1-deficient cells. Collectively, these findings establish an essential, epithelial cell-intrinsic role for SOCS1 in maintaining prostate tissue homeostasis by restraining proliferation, regulating lineage plasticity, limiting inflammation and oxidative stress, and conferring protection against genotoxic injury and neoplastic transformation.

cancer biology↗