Ligand-receptor dissociated expression explains high TSLP without prognostic impact in human primary head and neck squamous cell carcinoma.

Thymic stromal lymphopoietin (TSLP) is an interleukin (IL)-7-like cytokine expressed by epithelial cells during allergic inflammation, and activating dendritic cells (DC). Its expression and functional role in cancer remain controversial. We conducted retrospective (n = 89), and prospective studies including patients with untreated primary head and neck squamous cell carcinoma (HNSCC). We found that TSLP was overexpressed by HNSCC tumor cells, and associated with a highly differentiated status. However, no significant difference in overall and recurrence-free survival was found between patients bearing a tumor with high and low TSLP levels, respectively. Surprisingly, there was no significant association between the levels of TSLP expression, and the number of tumor-infiltrating mature DCLAMP(+) DC. In order to explain the apparent lack of TSLP-induced DC activation, we performed phenotypic and functional experiments on freshly resected tumors. Tumor-infiltrating immune cells, including DC, did not express the TSLP receptor heterodimer (TSLPR chain, IL-7Ralpha chain). Furthermore, freshly sorted blood CD11c(+) DC from healthy donors cultured with tumor-conditioned supernatant exhibited an activated profile, but this was not affected by an anti-TSLP blocking antibody, suggesting a DC activation pathway independent of tumor-derived TSLP. Overall, our results demonstrate that TSLP is overexpressed in HNSCC but its function is hampered by the lack of TSLPR-expressing cells in the tumor microenvironment. Such a dissociated ligand-receptor expression may impact intercellular communication in other immune activation pathways, and tumor types.

[Work ability in cancer patients: Six years assessment after diagnosis in a cohort of 153 workers]. / Travailler après un cancer: bilan 6 ans après la reprise Analyse d'une cohorte de 153 salariés.

PURPOSE: If several studies analyse the working abilities of cancer survivors two years after the diagnosis, few of them analyse the long term becoming at work of these patients. Here we study a cohort of 153 workers, 6 years after they returned to work after experiencing a cancer in 2005 or 2006. All these workers participated in a previous study realised in 2008, two years after the diagnosis. MATERIAL AND METHODS: Fourty occupational physicians included 153 workers out of the 319 particpating in a first study conducted in 2008. Two questionnaires were completed by both the worker and the occupationnal physician. Twenty four patients' interviews and nine physician's interviews were also realized for qualitative analysis. RESULTS: Six years after they returned to work, 46% were still working in the same company. Among patients aged less than 55 years (113 out of 153), they were 20% to leave the company (a 4% annual rate). Concerning the 83 salaries still at work, sequelaes of the disease are often still present: fatigue (57%), sleep disorders (56% vs 34% at 2 years), memory and concentration disorders (34%) and chronic pain (16%). Thirty one percent reported serious anxious disorders vs 29% in 2008. Difficulties are still present in 71% of the responders. Fourty percent of the nonexecutive workers feeled penalized. Qualitative study shows that a successfull return to work is associated with a friendly environement, the support of the company, and a long term accompagnying policy. CONCLUSIONS: Six years after returning to work, one employee out of two is still working in the same company. Far to disappear, the identified difficulties two years after the diagnosis are still present, long time after stopping the treatments. A successfull return to work needs an important support from both the company and the co-workers.

Two types of squamous cell carcinoma of the palatine tonsil characterized by distinct etiology, molecular features and outcome.

To determine whether human papillomaviruses (HPV) positive tonsillar squamous cell carcinoma (SCC) represent a specific entity, we studied the prevalence of HPV association and of tobacco/alcohol exposure in a series of 52 cases of tonsillar SCC cases. p53, p16, and pRb levels, deregulated by viral oncoproteins were assessed. Forty patients reported tobacco/alcohol exposure, 10 reported no exposure. HPV DNA was found in 32/52 (62%) cases, (HPV16 genotype in 27). All patients with no history of tobacco-alcohol exposure presented HPV positive tumor (p=0.0008). A strong correlation was observed between positive HPV status, decrease in pRB and increase in p16 expression level. 5 year overall survival rate was higher in HPV16 positive patients than in HPV negative (71% versus 36%; p=0.023). HPV status remained a significant prognostic factor in multivariate analysis. Tonsillar SCC can thus be divided in HPV positive and negative subgroups with different oncogenesis and response to treatment.