Identification of CD8+CD25+Foxp3+ suppressive T cells in colorectal cancer tissue.

International audienceBACKGROUND: The antitumoral immune response is one determinant of colorectal cancer (CRC) outcome. Recent work suggests that Foxp3(+)CD25(+)CD4(+) regulatory T cells (T4reg) might hamper effective immunosurveillance of emerging cancer cells and impede effective immune responses to established tumours. In this descriptive study, we analysed blood and tissue regulatory T cell populations in patients with CRC. METHODS: Blood and tissue regulatory Foxp3(+) T cells from 40 patients with CRC were compared to regulatory Foxp3(+) T cells from normal colonic tissue and from blood of 26 healthy volunteers. Flow cytometry was used to quantify and phenotype all Foxp3(+) T cell populations. Correlations were sought with the tumour stage and with micro-invasive status. The suppressive capacity of regulatory Foxp3(+) T cells was assessed by their effect on CD4(+)CD25(-) T cell proliferation in vitro and by their capacity to inhibit cytokine production by conventional T cells. RESULTS: We found a significant increase of CD8(+)CD25(+)Foxp3(+) cells (T8reg) in blood and CRC tissue; their phenotype was close to that of T4reg. T8reg cells infiltrating CRC were activated, as suggested by increased cytoxic T lymphocyte-associated antigen-4, glucocorticoid-induced tumour necrosis factor-related protein, and transforming growth factor (TGF)beta1 expression compared to T8reg from normal autologous colonic tissue. Moreover, T8reg were able to suppress CD4(+)CD25(-) T cell proliferation and Th1 cytokine production ex vivo, demonstrating that tumour-infiltrating T8reg have strong suppressive capacities. T8reg numbers correlated with the tumour stage and with micro-invasive status. Finally, interleukin 6 and TGF beta 1 synergistically induced the generation of CD8(+)CD25(+)Foxp3(+) T cells ex vivo. CONCLUSIONS: We have identified a new regulatory T cell population (CD8(+)Foxp3(+)) in colorectal tumours. After isolation from cancer tissue these CD8(+)Foxp3(+) cells demonstrated strong immunosuppressive properties in vitro. These data suggest that these cells may contribute to tumoral immune escape and disease progression

Efficacité et tolérance de la radiothérapie externe pour les patients atteints d'une récidive d'un carcinome différencié de la thyroïde

International audiencePurposeRadiation therapy is often the last resource treatment for cervical relapse in iodine refractory differentiated thyroid cancer. We present locoregional control data in patients with cervical relapse treated with curative intent radiation therapy with or without concomitant carboplatin.Material and methodsThis monocentric retrospective study gathered data on patients with differentiated thyroid carcinoma – vesicular or papillary – in relapse after thyroidectomy who received a curative intent cervical radiation therapy. Locoregional progression free survival (LRPFS), progression free survival (PFS), overall survival (OS) were gathered as well as acute and chronic adverse events assessed with the CTCAE v4.ResultsThirty-nine patients were consecutively included between 2005 and 2019. The median follow-up was 36.6 months. Fifteen patients (38%) had a locoregional relapse, locoregional control at 2 years was 66.7%. The median LRPFS was 48 months [32.9–not reached] and the median overall survival 49 months [38.8–not reached]. In multivariate analysis, initial incomplete resection was associated with poorer OS (HR: 24.39 [3.57–166.78], P = 0.00113) and LRPFS (HR: 33.91 [4.46–257.61], P = 0.00066), extra nodal spread was associated with poorer LRPFS (HR: 13.45 [1.81–99,76], P = 0.011). ECOG performance status was associated with OS (HR: 5.11 [1.57–16.66], P = 0.00688). Carboplatin association with radiation therapy was not associated with improved survivals (OS: P = 0.34, LRPFS: P = 0.84). The rate of acute grade 3 toxicities was 14%.ConclusionSalvage cervical radiation therapy was associated with a locoregional control of 66.7% at 2 years with a reasonable toxicity rate. Carboplatin association with radiation therapy did not improve locoregional control nor overall survival in comparison with radiotherapy alone.Objectif de l’étudeLa radiothérapie est souvent d’indication tardive pour les carcinomes différenciés de la thyroïde en rechute réfractaire à l'iode. L’objectif de cette étude était de décrire l’efficacité et la toxicité de la radiothérapie cervicale de rattrapage associée ou non à une chimiothérapie concomitante par carboplatine.Matériel et méthodesCette étude rétrospective monocentrique a collecté les données de patients atteints d’un carcinome différencié de la thyroïde, en situation de rechute après thyroïdectomie, vésiculaire ou papillaire, ayant reçu une radiothérapie cervicale à dose curative. Le critère principal évalué était le contrôle locorégional. Les critères secondaires étaient la survie sans rechute, la survie globale et la toxicité aiguë et chronique évaluée selon la Common Terminology Criteria for Adverse Events (CTCAE) v4.RésultatsTrente-neuf patients consécutifs ont été traités entre 2005 et 2019. Le suivi médian était de 36,6 mois. Quinze cancers (38 %) ont rechuté locorégionalement. La probabilité de contrôle locorégional à 2 ans était de 66,7 %. La survie sans récidive locorégionale médiane était de 48 mois [32,9–non atteinte] et la survie globale médiane de 49 mois [38,8–non atteinte]. En analyse multifactorielle, la résection incomplète initiale était associée à la survie globale (hazard ratio [HR] : 24,39 [3,57–166,78], p = 0,00113) et à la survie sans récidive locorégionale (HR : 33,91 [4,46–257,61], p = 0,00066). La rupture capsulaire initiale était associée à la survie sans rechute locorégionale (HR : 13,45 [1,81–99,76], p = 0,011). Le score sur l'échelle de statut de performance de l'ECOG était associé à la survie globale (HR : 5,11 [1,57–16,66], p = 0,00688). Les survies des patients pris en charge par chimioradiothérapie concomitante et par radiothérapie exclusive n’étaient pas significativement différentes (survie globale : p = 0,34 ; survie sans récidive locorégionale : p = 0,84). Une toxicité aiguë de grade 3 a été rapportée dans 14 % des cas.ConclusionLa radiothérapie cervicale de rattrapage est associée à un taux de contrôle locorégional de 66,7 % à deux ans, au prix d’une toxicité acceptable. L’adjonction de carboplatine concomitant à la radiothérapie ne semble pas améliorer le taux de contrôle locorégional ni celui de survie globale par rapport à la radiothérapie exclusive

Gender-related differences in MEN1 lesion occurrence and diagnosis: a cohort study of 734 cases from the Groupe d''etude des Tumeurs Endocrines

International audienceCONTEXT: Multiple endocrine neoplasia type 1 (MEN1) disease is an autosomal dominant syndrome that is believed to equally affect men and women. This assumption has never been confirmed. OBJECTIVE: The aims of this study were to evaluate the impact of gender on the prevalence of MEN1 lesions, on their lifetime probability of occurrence, and on the diagnosis of MEN1. DESIGN: Data regarding a study of 734 cases of MEN1 from the multicenter 'Groupe d'étude des Tumeurs Endocrines' were analyzed. RESULTS: There were 57.8% females. The prevalence and probability of pancreatic tumors were higher in males than in females (P=0.06, P=0.0004). This difference was due to gastrinomas. The prevalence and probability of developing pituitary tumors were significantly greater in females (P<0.001, P<0.0001). Thymic tumors were exclusively found in men. There were no significant gender differences in the prevalence and the probability of developing hyperparathyroidism, or adrenal and bronchial tumors, or in the proportion of positive genetic tests. A family history of MEN1 was more frequently found in men than in women at the time of diagnosis (P=0.02). In the case of pituitary tumor, the proportion of patients diagnosed with MEN1 at the time of the first lesion was lower in women (44.2%) than in men (67.3%). CONCLUSION: The phenotype expression of the MEN1 disease gene was different in males and females. In female patients, the possibility of MEN1 is not sufficiently taken into account. Any patient presenting a lesion that belongs to the MEN1 spectrum, such as a pituitary tumor, should be closely questioned about their family history and should be tested for hypercalcemia