The CTSZ/TRA2A/IL-32/ITGA5 axis orchestrates protumoral immunity in PCa metastasis by driving M2-TAM recruitment. Targeting this pathway, particularly through ITGA5 blockade, represents a promising therapeutic strategy to inhibit metastatic progression and remodel the immunosuppressive tumor microenvironment.

In animal studies, co-injection of cancer cells with PCs compromises TKI effectiveness, independently of blood vessel functions, while inhibition of β5-integrin restores tumor cell sensitivity. Overall, the findings highlight direct crosstalk between cancer cells and pericytes, impacting TKI sensitivity via IL32-β5-integrin paracrine signaling, proposing an enhanced therapeutic approach for EGFR-mutated patients.

Using inhibitors of protein secretion pathways and serial (ultra)centrifugation of T cell supernatants, we demonstrate that T cells actively secrete IL-32β unconventionally, as a free protein and, to a minor degree, through exosomes. Thus, our data identify activated T cells as major IL-32β secretors in health and cancer.

Lentivirus overexpressing IL-32 or knocking down Fat atypical cadherin 4 (FAT4), yes-associated protein (YAP) inhibitor-Verteporfin (VP) were used to treat human NP cells, to explore the pathogenesis of IL-32...Mechanistically, the elevation of IL-32 in the inflammatory microenvironment enhanced its interactions with FAT4 and mammalian sterile 20-like kinase1/2 (MST1/2) proteins, prompting MST1/2 phosphorylation, and activating the Hippo/YAP signaling pathway, causing matrix metabolism disorder in NP cells. Our results suggest that IL-32 mediates matrix metabolism disorders in NP cells in the inflammatory micro-environment via the FAT4/MST/YAP axis, providing a theoretical basis for the precise treatment of IDD.

Finally, using quantitative reverse transcription polymerase chain reaction, interleukin-32 and miR-205 expression levels were significantly lower in the placentas of patients with pregnancy-induced hypertension than in women with normal pregnancies. In conclusion, interleukin-32 regulates trophoblast invasion through the miR-205-nuclear factor kappa B-MMP2/9 pathway, which is involved in pregnancy-induced hypertension.

rhIL-32θ induced nuclear translocation of the NF-κB via regulation of the MAPK (p38) pathway. In conclusion, point-mutated rhIL-32θ induced the polarization to M1-like macrophages through the MAPK (p38) and NF-κB (p65/p50) pathways.

Treatment with BAY11-7082 (an NFκB inhibitor) notably decreased miR-205 expression but had no effect on IL-32 levels...Knockdown of IL-32 significantly inhibited the migration and invasion of HeLa and SiHa; conversely, treatment with rIL-32α and rIL-32γ notably promoted their migration and invasion. In brief, IL-32 is highly expressed via the formation of a positive regulatory loop with NFκB/miR-205, contributing to the persistence of inflammation and promoting the progression of cervical cancer.

GO enrichment analysis showed that IL32 expression was associated with cancer pathways, cytokine-receptor interactions, and NOD-like receptor signaling pathways. These findings suggest that IL32 may serve as a biomarker of cancer immune infiltration and poor prognosis, providing new therapeutic targets for cancer treatment.

In conclusion, IL-32 potentially induced by inflammatory conditions and anticancer therapy and contribute to immune escape of cancer cells via development the immunosuppressive microenvironment. IL-32 might be a target molecule for anti-cancer therapy.

Moreover, it assessed the significance of aberrant IL-32 expression in associated diseases and analyzed the effects of IL-32 on four key types of cancer: Colorectal, gastric, breast and lung. However, the mechanism of action of IL-32 needs to be further demonstrated by assessing the role of this cytokine in cancer to elucidate novel and reliable targets for future cancer treatments.

Rescue experiments were conducted to demonstrate that CAF-exosomes promoted biological behaviors of GC cells by upregulating IL32 and downregulating ESR1 expression. In conclusion, CAF-derived exosomes promote GC cell viability, migration, and invasion by elevating the IL32/ESR1 axis, suggesting a novel strategy for metastatic GC treatment.

IL-32 was detected in hepatoblastoma cell lines, but not in all hepatoblastoma patients. We hypothesized that stimulation such as chemotherapy might induce expression of IL-32, which might be a critical mediator of chemoresistance in hepatoblastoma through inducing protumor activation in macrophages.