Reduced MHC Class I and II Expression in HPV−Negative vs. HPV−Positive Cervical Cancers

Abstract

Cervical cancer (CC) is the second most common cancer in women worldwide and the fourth leading cause of cancer-associated death in women. Although human papillomavirus (HPV) infection is associated with nearly all CC, it has recently become clear that HPV−negative (HPV−) CC represents a distinct disease phenotype with increased mortality. HPV−positive (HPV+) and HPV− CC demonstrate different molecular pathology, prognosis, and response to treatment. Furthermore, CC caused by HPV α9 types (HPV16-like) often have better outcomes than those caused by HPV α7 types (HPV18-like). This study systematically and comprehensively compared the expression of genes involved in major histocompatibility complex (MHC) class I and II presentation within CC caused by HPV α9 types, HPV α7 types, and HPV− CC. We observed increased expression of MHC class I and II classical and non-classical genes in HPV+ CC and overall higher expression of genes involved in their antigen loading and presentation apparatus as well as transcriptional regulation. Increased expression of MHC I-related genes differs from previous studies using cell culture models. These findings identify crucial differences between antigen presentation within the tumor immune microenvironments of HPV+ and HPV− CC, as well as modest differences between HPV α9 and α7 CC. These differences may contribute to the altered patient outcomes and responses to immunotherapy observed between these distinct cancers.

Effects of Dietary Steroid Saponins on Growth Performance, Serum and Liver Glucose, Lipid Metabolism and Immune Molecules of Hybrid Groupers (♀Epinephelus fuscoguttatus × ♂Epinephelus lanceolatu) Fed High-Lipid Diets

“…In a similar trend, higher expressions of mhc II , il-10 and tgf-β genes and lower expressions of inf-γ , il-6 and tnf-α genes in the liver were found in turbot [ 43 ], sea bream [ 44 ] and carp [ 45 , 46 ] fed the diet with saponins. The expression of mhc II in the antigen presentation pathway might be upregulated by the saponins in groupers, which enables T cells to recognize antigens [ 47 ], together with the higher expression of il-10 and tgf-β genes to exhibit the anti-inflammation in the body’s immune system. Saponins could act on the NF-κB signaling pathway to play a role in inflammation in the enterocytes [ 48 ] and also enhance the antioxidant capacity of carp [ 45 ] and mice [ 49 ] by acting on the Nrf2 signaling pathway and upregulating sod , cat and gr gene expressions, which then alleviate the liver damage.…”

Bioinformatics analysis of immune characteristics in tumors with alternative carcinogenesis pathways induced by human papillomaviruses

“…In the immune-related genes, we took a closer look at the genes that encode proteins that are critical for immune cell infiltration (chemokines and their ligands) and the efficacy of antitumor immunity (immune checkpoints and components of APP pathways). Comparison of HPV + and HPV − CCs has shown increased expression of APP genes and genes encoding immune checkpoints and markers of immune cells in HPV + tumors [ 44 , 45 ]. Since the E7 oncoprotein downregulates the expression of MHC class I genes and these genes were also upregulated in HPV + tumors, the increased expression of the followed genes in HPV + tumors was probably associated with higher immune cell infiltration and interferon (IFN)-γ production.…”

SLC7A11, a potential immunotherapeutic target in lung adenocarcinoma

“…MHCs are divided into two categories: MHC-I and MHC-II. MHC-I and MHC-II interact with CD8+ T cells and CD4+ T cells respectively, thus activating the immune response 33 , 34 . Tumour cells usually express abnormal MHC-I molecules, which allows them to escape attack by CD8+ T cells.…”