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Auto-immunity and inflammation are risk factors of cancer (WP2)

Risk of cancer in Autoimmune Diseases and Inflammatory Diseases. Risks, implications and evolution, drugs and new perspectives in cancer immune surveillance.

WP 2 Leader : Raphaèle Seror

  • The factors involved in the risk of lymphoma in SS, RA and lupus are studied (Xavier Mariette and Laurence Meyer). We combine epidemiological studies (with access to cohorts and to SNIIRAM (social security data from all French population) and translational studies with samples from patients included in the cohorts (Céline Verstuyft).
  • Other types of cancer may be more frequent in the context of AID/ID and the risk factors of these cancers are studied (Aurélien Marabelle, Benjamin Besse, Franck Carbonnel, Dominique Lamarque, Caroline Robert and Isabelle Bourgault-Villada): digestive cancers and IBD, cutaneous cancers and psoriasis. Some epidemiological and mechanistic studies are conducted for understanding this transition between AID/ID and cancer. Chronic inflammation is a major risk factor of cancer in these AID/ID and is also seen in chronic HIV infection, also associated with an increased risk of cancer. Cohorts of patients with HIV infection and their biobanks, are available in FHU CARE (Olivier Lambotte and Laurence Meyer) and are available as comparators.

Benjamin Besse is the coordinator of the RYTHMIC network with a large database of patients with thymic malignancies. These cancers are frequently associated with AID and a specific study is performed with long term immuno-monitoring of these patients (Nathalie Chaput-Gras) for assessing the frequency and the mechanisms.

Beside activity of the AID/ID, another cause of the increased risk of cancer in AID/ID is a defect of immune surveillance induced by immunosuppressive drugs used in AID and also in transplantation. We have preliminary results in different fields and share this data for better evaluating the oncogenic risk of immunosuppressive drugs and to better understand the mechanisms of cancer immune surveillance altered by these drugs:

  • Immuno-suppressive drugs used in transplantation and cancer. This question has been studied by Antoine Durrbach who participated in the development of Belatacept (CTLA4-Ig) in the prevention of renal graft reject. This drug, which is the converse of Ipilimumab (anti-CTLA4 Ab) may increase the risk of EBV-associated lymphoma. This team explores risk of other immunosuppressive drugs given in the context of transplantation.
  • The risk of cancer with TNF inhibitors (TNFi) in IBD. Franck Carbonnel has demonstrated that TNFi in IBD were associated with an increased risk of lymphoma. The effect of TNFi on other types of cancer is studied.
  • The risk of cancer with TNFi and other biologics in rheumatic diseases. A close study led Xavier Mariette, using the French social security data from SNIIRAM (all French population) is done to compare the risk of cancer in patients treated for RA, spondyloarthritis or psoriatic arthritis with different types of TNFi and other biologics.
  • The effect of TNFi on macrophages. Xavier Mariette found in a mouse model of AID-associated lymphoma (BAFF transgenic mice) an increased risk of lymphoma with monoclonal anti-TNF antibodies but not with the TNF soluble receptor (submitted). Preliminary data suggesting that monoclonal anti-TNF antibody may have deleterious effect on macrophage cancer immune surveillance is confirmed (Xavier Mariette and Jean-Luc Perfettini).

Timetable, deliverables and other proposed indicators

  • D2.1.1: New predictive factors of lymphoma in RA, lupus and SS
  • D2.1.2: Risk and predictive factors of digestive cancers in IBD
  • D2.1.3: Risk and predictive factors of cutaneous cancer in psoriasis

  • D2.2.1: Predictive factors of AID in patients with thymic malignancies

  • D2.3.1: Estimation of the risk of cancer induced by TNF inhibitors in IBD
  • D2.3.2: Estimation of the risk of cancer induced by TNF inhibitors and other biologics in RA
  • D2.3.3: Mechanism of action of TNF inhibitors on macrophage immune surveillance
  • D2.3.4: Estimation of the risk of cancer induced by anti-rejection drugs in transplantation