Castagna, A. | Search bioRxiv

bioRxiv2024

Tumor-associated macrophages enhance tumor innervation and spinal cord repair

AO_SCPLOWBSTRACTC_SCPLOWTumor-associated macrophages (TAM) enhance cancer progression by promoting angiogenesis, extracellular matrix (ECM) remodeling, and immune suppression. Nerve infiltration is a hallmark of various cancers and is known to directly contribute to tumor growth. However, the role of TAM in promoting intratumoral nerve growth remains poorly understood. In this study, we demonstrate that TAM expressed a distinct "neural growth" gene signature. TAM actively enhance neural growth within tumors and directly promote neurites outgrowth. We identify secreted phosphoprotein 1 (Spp1) as a key mediator of TAM-driven neural growth activity, which triggers neuronal mTORC2 signaling. Leveraging this new neural growth function, which added to the TAM wound healing properties, we explored TAM potential to repair central nervous system. Adoptive transfer of in vitro-generated TAM in a severe complete-compressive-contusive spinal cord injury (scSCI) model, not only repaired the damaged neural parenchyma by improving tissue oxygenation, ECM remodeling, and dampening chronic inflammation, but also resulted in neural regrowth and partial functional motor recovery. Proteomic analysis and subsequent functional validation confirmed that TAM-induced spinal cord regeneration is mediated through the activation of neural mTORC2 signaling pathways. Collectively, our data unveil a previously unrecognized role of TAM in tumor innervation, neural growth, and neural tissue repair.

neuroscience↗

bioRxiv2023

Is HDL-c plasma concentration a possible marker of HIV replication? A cross-sectional analysis in untreated HIV-infected individuals accessing HIV care in Italy

AimsHIV infection is associated with dyslipidemia and an increased risk for cardiovascular diseases. HIV Nef protein downregulates the generation of nascent HDL. The interplay between HIV-RNA, HDL-c level and CD4/CD8 ratio in naive HIV patients remains to be elucidated. MethodsWe included untreated persons living with HIV (PLWH) of the ICONA Foundation Study cohort if they also had [≥]2 viral load (VL) measurements prior to ART initiation. We performed unadjusted correlation and linear regression analyses evaluating the effect of VLset on HDL-C. Vlset and CD4/CD8 ratio were fit in the log10 scale, while HDL-c, was fitted in the untransformed raw scale. ResultsWe included 3,980 untreated PLWH. Fifty-eighty (1.5%) were aviremic. We observed a negative correlation between HDL-c and VLset (Pearson R2=0.03), from fitting an unadjusted linear regression model -8.5 mg/dl (95% CI: -15,9 --0,84 p<0.03). There was a dose-response relationship between HDL-c levels and VLset, however, this association was somewhat attenuated after further controlling for gender. Despite a positive correlation between HDL-c and CD4/CD8 ratio, the HDL-c plasma concentration does not satisfy the criteria for a strong surrogate marker. ConclusionsOur data show that HDL-c plasma concentration is significantly lower per higher level of VLSet although this was in part explained by gender. Further analyses should be promoted to better understand the molecular mechanisms that underline the relationship between HIV replication, HDL-c formation, and diseases progression.

immunology↗