Cervical Cancer Neoantigen Landscape and Immune Activity is Associated with Human Papillomavirus Master Regulators

Area of Science:

• Oncology
• Immunology
• Genetics

Background:

• Human papillomaviruses (HPVs) are linked to cervical cancer development, with HPV oncoproteins as immunotherapy targets.
• Current HPV-based immunotherapies have limitations in patient benefit and treatment durability.
• Neoantigens from somatic mutations present a distinct immunotherapy strategy for HPV-associated cancers.

Purpose of the Study:

• To investigate the landscape of neoantigens in cervical cancer.
• To analyze the correlation between mutation/neoantigen load and antigen presentation, immune cell infiltration, and HPV-induced gene expression.
• To identify potential novel therapeutic targets within HPV master regulators.

Main Methods:

• Prediction of all possible mutated neopeptides from two large sequencing datasets.
• Analysis of correlations between neoantigen load, antigen presentation, immune cell types, and HPV-induced gene expression signatures.
• Assessment of HPV master regulator associations with mutation load, neoantigen load, and immune microenvironment components.

Main Results:

• Targetable neoantigens were detected in the majority of cervical tumors.
• Recurrent immunogenic mutated peptides were identified in key oncogenic driver genes (e.g., KRAS, PIK3CA).
• HPV-induced master regulators correlate with mutation/neoantigen load and immune-suppressive molecules (PD-L1, TGFB1, IL-10), potentially hindering anti-tumor immunity.

Conclusions:

• Neoantigens represent a promising complementary immunotherapy approach for cervical cancer.
• HPV master regulators are implicated in modulating the tumor immune microenvironment and may be involved in immune evasion.
• Targeting HPV master regulators could be a potential therapeutic strategy for cervical cancer.