Host immune responses to cervical cancer

The purpose of this review is to understand the role of the host immune system in clearing the human papillomavirus (HPV) infection, strategies adopted by HPV to subvert the host immune responses and analyze the challenges to the future immunotherapeutic treatment modalities.

Cervical epithelium provides a protective niche to the virus to subvert the immune responses. The absence of an inflammatory milieu in the cervix makes the resident dendritic and langerhan cells tolerogenic to HPV antigens. CD4 cells predominated in regressing cervical intraepithelial neoplasia lesions, whereas CD8 cells were dominant in invasive carcinoma. A reduced expression of T cell signaling molecule T-cell receptor zeta chain was observed in CD8 lymphocytes. Decreased numbers of NKG2D expressing natural killer and T cells were present in patients with cervical cancer and cervical intraepithelial neoplasia. Increased frequencies of CD4 CD25+ FoxP3+ T regulatory cells were observed in patients with cervical cancer. The Nrp-1+Treg showed greater suppressive activity. A network of Treg and indoleamine 2, 3-dioxygenase expressed in tumor cells facilitates immune escape of tumor cells.

The HPV uses different strategies to evade immune recognition. Understanding the immune evasion mechanisms used by HPV will help in designing newer therapeutic strategies for cervical cancer.