Although understanding of T cell exhaustion is widely based on mouse models, its analysis in patients with cancer could provide clues indicating tumor sensitivity to immune checkpoint blockade (ICB). Data suggest a role for costimulatory pathways, particularly CD28, in exhausted T cell responsiveness to PD 1/PD L1 blockade. Here, we used single cell transcriptomic, phenotypic, and function al approaches to dissect the relation between cos + T cell exhaus tion, CD28 costimulation, and tumor specificity in head and neck, cervical, and ovarian cancers. We found that memory tumor specific cos + T cells, but not bystander cells, sequentially express immune checkpoints once they infiltrate tumors, leading, in situ, to a functionally exhausted population. Exhausted T cells were none
Surgical resection followed by radiotherapy can be considered like the optimal treatment modality for limited esthesioneuroblastoma. However, therapeutic management of locally advanced tumors remains a challenge. The aim of our study was to access and compare the oncologic results of the different treatment modalities in advanced esthesioneuroblastoma. We performed a systematic review using the Medline, and Cochrane database in accordance with PRISMA criteria and included all the cases of advanced esthesioneuroblastoma published between 2000 and 2013. We also retrospectively included 15 patients with an advanced esthesioneuroblastoma managed at our tertiary care medical center. Long-term survival rates defined as the time from diagnosis or randomization to the date of death or last follow-up were evaluated for each treatment with Kaplan-Meier survival curve analyses. 283 patients have been included. The mean follow-up was 78 months. Five-year highest survival rates were obtained in patients treated by surgery associated with radiotherapy. Ten-year highest survival rates were obtained in patients treated by the association of surgery, radiotherapy and chemotherapy (p = 0.0008). Within the surgical group, 5-year highest survival rates were obtained in patients treated by endoscopic resection (p = 0.003). Surgical resection combined with radiotherapy offers the gold standard of care. Adjuvant chemotherapy seems to improve the long-term survival in patients with locally advanced esthesioneuroblastoma. Endoscopic resection in advanced tumors should be discussed on a case-by-case basis.
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