How immunodeficiency can lead to malignancy.

Area of Science:

• Immunology
• Oncology
• Virology

Background:

• Immunodeficiency, acquired (e.g., HIV) or congenital (inborn errors of immunity - IEIs), leads to increased malignancy risk.
• The specific cancers observed correlate with the underlying immune defects.
• Understanding these links is crucial for managing cancer in immunocompromised individuals.

Observation:

• CD4+ T-cell lymphopenia in people living with HIV (PLWH) and certain IEIs predisposes to aggressive B-cell non-Hodgkin lymphomas.
• Profound T-cell deficiency or dysfunction increases risk for cancers linked to oncogenic viruses like KSHV, EBV, HPV, and Merkel cell polyomavirus.
• Impaired natural killer cell function in IEIs strongly associates with HPV-driven epithelial cancers.
• Defects in DNA repair pathways contribute to both hematologic and nonhematologic cancers by affecting immune cell development and DNA damage responses.

Findings:

• Immunodeficiency significantly alters cancer profiles, favoring specific lymphoma subtypes and virus-associated malignancies.
• The type and severity of immune defect dictate the spectrum of associated cancers.
• DNA repair pathway defects represent a distinct mechanism contributing to cancer development in immunodeficiency.

Implications:

• Cancer treatment in immunodeficient patients should aim for cure and involve close collaboration between oncologists, immunologists, and infectious disease specialists.
• Recognizing the specific immune defects is key to predicting and managing cancer risks.
• Further research into the molecular mechanisms underlying these associations can inform novel therapeutic strategies.