Stereotaxic administrations of allogeneic human Vγ9Vδ2 T cells efficiently control the development of human glioblastoma brain tumors

International audienceGlioblastoma multiforme (GBM) represents the most frequent and deadliest primary brain tumor.Aggressive treatment still fails to eliminate deep brain infiltrative and highly resistant tumor cells.Human Vg9Vd2 T cells, the major peripheral blood gd T cell subset, react against a wide array oftumor cells and represent attractive immune effector T cells for the design of antitumor therapies.This study aims at providing a preclinical rationale for immunotherapies in GBM based on stereotaxicadministration of allogeneic human Vg9Vd2 T cells. The feasibility and the antitumor efficacy ofstereotaxic Vg9Vd2 T cell injections have been investigated in orthotopic GBM mice model usingselected heterogeneous and invasive primary human GBM cells. Allogeneic human Vg9Vd2 T cellssurvive and patrol for several days within the brain parenchyma following adoptive transfer and cansuccessfully eliminate infiltrative GBM primary cells. These striking observations pave the way foroptimized stereotaxic antitumor immunotherapies targeting human allogeneic Vg9Vd2 T cells in GBMpatients

High Risk of Anal and Rectal Cancer in Patients With Anal and/or Perianal Crohn’s Disease

International audienceBackground & AimsLittle is known about the magnitude of the risk of anal and rectal cancer in patients with anal and/or perineal Crohn’s disease. We aimed to assess the risk of anal and rectal cancer in patients with Crohn’s perianal disease followed up in the Cancers Et Surrisque Associé aux Maladies Inflammatoires Intestinales En France (CESAME) cohort.MethodsWe collected data from 19,486 patients with inflammatory bowel disease (IBD) enrolled in the observational CESAME study in France, from May 2004 through June 2005; 14.9% of participants had past or current anal and/or perianal Crohn’s disease. Subjects were followed up for a median time of 35 months (interquartile range, 29–40 mo). To identify risk factors for anal cancer in the total CESAME population, we performed a case-control study in which participants were matched for age and sex.ResultsAmong the total IBD population, 8 patients developed anal cancer and 14 patients developed rectal cancer. In the subgroup of 2911 patients with past or current anal and/or perianal Crohn’s lesions at cohort entry, 2 developed anal squamous-cell carcinoma, 3 developed perianal fistula–related adenocarcinoma, and 6 developed rectal cancer. The corresponding incidence rates were 0.26 per 1000 patient-years for anal squamous-cell carcinoma, 0.38 per 1000 patient-years for perianal fistula–related adenocarcinoma, and 0.77 per 1000 patient-years for rectal cancer. Among the 16,575 patients with ulcerative colitis or Crohn’s disease without anal or perianal lesions, the incidence rate of anal cancer was 0.08 per 1000 patient-years and of rectal cancer was 0.21 per 1000 patient-years. Among factors tested by univariate conditional regression (IBD subtype, disease duration, exposure to immune-suppressive therapy, presence of past or current anal and/or perianal lesions), the presence of past or current anal and/or perianal lesions at cohort entry was the only factor significantly associated with development of anal cancer (odds ratio, 11.2; 95% CI, 1.18-551.51; P = .03).ConclusionsIn an analysis of data from the CESAME cohort in France, patients with anal and/or perianal Crohn’s disease have a high risk of anal cancer, including perianal fistula–related cancer, and a high risk of rectal cancer