Immune Response Modulation by HPV16 Oncoproteins in Lung Cancer: Insights from Clinical and In Vitro Investigations

Abstract

Lung cancer has the highest mortality rates worldwide, and Human Papillomavirus (HPV) has been associated with its carcinogenesis. In this study, HPV16 genes’ expressions were investigated in patient samples, along with the immunological response promoted by lymphocytes and monocytes in A549 cells transfected with HPV oncogenes and co-cultured with PBMC. An increase in the expression of E5 was observed in the patients’ samples. In the in vitro analysis, a decrease in the number of monocytes and cytotoxic cells was observed when co-stimulated by E6 and E7, and it promoted an increase in the Th2 profile. In contrast, the high proliferation of cytotoxic cells in A549 cells transfected with E5, associated with the high expression of costimulatory molecules in monocytes, suggests a low capacity of E5 to inhibit the presentation of antigens by antigen-presenting cells (APC) and a possible use of E5 in future therapeutic strategies against lung cancers associated with HPV.

Keywords

• lung cancer
• HPV oncogenes
• immune cell interaction
• cancer cell signaling
• macrophages and lymphocytes