Fig. 8: A scheme summarizing our main findings and a proposed model.

A Clinical relevance. High levels of Hpa2 in cervical carcinoma (CC) lesions, or in cells that comprise the tumor microenvironment (TME) are associated with low tumor grade and good prognosis. B Experimental approaches. Overexpression on Hpa2 and the 140/543 mutants in SiHa cervical carcinoma cells results in smaller tumors associated with lower levels of Erk phosphorylation, and increased incidence of nuclear BRD7 and histone acetylation on lysine 9. C Macrophage polarization. In the absence of Hpa2 (Hpa2-KO), macrophages are shifted towards M2 polarization, exerting increased phagocytic, chemoattraction, and angiogenic capacities. D Co-implantation. Co-injection of SiHa cells together with Hpa2-KO macrophages resulted in bigger and more vascularized tumors vs tumors produced by SiHa cells implanted with control (wt) macrophages. Interestingly, foam-like macrophages were noted to accumulate adjacent to the tumor mass. Given the pro-tumorigenic properties of foam cells, this should be kept in mind in approaches utilizing macrophages as an anti-cancer tool.