Tumor microenvironment, inflammation and immunomodulation: therapeutic possibilities and prognostic markers

Abstract

Our laboratory has been investigating interactions between tumor and inflammatory cells, as well as systemic effects displayed by the tumor in its host. Our main focus has been Human papillomavirus (HPV) associated tumors. HPV infections are the main etiologic factor for the development of cervical cancer, as well as a percentage of other anogenital and oropharingeal cancers.We have recently shown that these tumors display effects on the host like leukocytosis, reduction of antigen presentation efficiency, reduction of NFºB activation in professional antigen presenting cells (APCs). While working in the tumor and inflammatory cells interactions to unravel the mechanisms behind these effects, we are also suggesting interfering in the above processes to inhibit tumor growth: neutralization of cytokines that may play a role in leukocytosis, activation of the NFºB pathway in APCs via treatment with CD40 agonist and test of their potential to activate antitumor responses in T cells. These studies are complementary to an ongoing study where we are characterizing the inflammatory infiltrate in cervical lesions of various grades. We have demonstrated that neutrophils infiltrate these lesions and, in cancer, their frequency is negatively correlated with CD8 T cells frequency. In this project, we intend to characterize the functional profile of these neutrophils and study their role in tumor progression. The results here obtained might be extrapolated to other HPV associated tumors or tumors with different etiologies. (AU)