The IDeATIon study: HIV impairs the immune response to lung cancer
People infected with HIV are more likely to develop lung cancer, in severe and poorly understood forms. A recent study, IDeATIon, shows that HIV impairs anti-tumour immunity, particularly CD8 T-cells, which are essential for fighting tumours. These findings could explain the poor prognosis for these cancers and support the therapeutic value of cancer vaccines in this context. The study was carried out in collaboration between Sorbonne University, the Sorbonne University Foundation, AP-HP (Assistance publique – Hôpitaux de Paris), Inserm (the French national Institute of Health and Medical Research) and the CANCERVIH network. Its findings have been published in the Journal of Thoracic Oncology.
Cancer cells are characterised by the presence of mutations in their DNA, which can lead to the production of abnormal molecules called tumour antigens. These become potential targets for the immune system in its fight against cancer. Lung cancer is one of the most common types of cancers worldwide and has a particularly poor prognosis among people living with HIV (PLHIV). However, the mechanisms underlying this worsening prognosis remain poorly understood. Identifying the factors which influence the frequency and severity of lung cancer among PLHIV could lead to improved and personalised care and treatment.
In this study, the genomic and immune characteristics of 27 lung cancers (from 15 PLHIV and 12 patients without immunodeficiency) were compared. A combination of broad-spectrum genomic, immunological and bioinformatic analyses were used to study tumour mutations, predict the types of antigens produced and evaluate the immune responses directed against them.
The tumour mutations and tumour antigens detected were generally similar in both groups. However, the immune responses differed significantly. In PLHIV, the immune response was limited to certain tumour antigens, while it was more varied and involved a wider range of antigens in patients without immunodeficiency. In particular, CD8 T-cells, which are considered to play a key role in anti-tumour responses, appear to be less active against tumour antigens in HIV-infected patients.
This is the first study to show the impact of HIV on the immunogenomic characteristics of lung cancer. These results show that tumour mutations are similar between PLHIV and patients without immunodeficiency, but that the presence of HIV weakens the immune response to certain tumour antigens. The study provides a potential explanation for the poor prognosis of lung cancer in PLHIV and paves the way for new therapeutic opportunities. The results suggest that immune therapies specifically targeting these tumour antigens could improve treatment for PLHIV.
This study brought together Sorbonne University, the Sorbonne University Foundation, AP-HP, Inserm, the Centre of Immunology and Microbial Infections (Inserm/CNRS/Sorbonne University), the CinBioS-UMS PASS Center for Informatics-Bioanalysis (Sorbonne University/Inserm) and the CANCERVIH network (certified and funded by the French National Cancer Institute). It is promoted by AP-HP and funded by the MSDAvenir endowment fund and the ARC Foundation for Cancer Research.
Find out more:
- Link to the article in the Journal of Thoracic Oncology.