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Escors, D.

Publications and source records attributed to Escors, D..

2 recordsLinked to original sources
bioRxiv2018

Radiopotentiation of Enzalutamide over Human Prostate Cancer Cells as Assessed by Real-Time Cell Monitoring

While radiotherapy is the first line of treatment for prostate cancer, androgen blockade therapies are demonstrating significant survival benefit as monotherapies. As androgen blockade can cause cell death by apoptosis, it is likely that androgen blockade will potentiate the cytotoxic activities of radiotherapy. Here we tested the potential synergistic effects of these two treatments over two human metastatic prostate cancer cells by real time growth monitoring (RTCA), androgen-sensitive LNCaP cells and androgen-resistant PC-3. Both cell lines were highly resistant to high doses of radiotherapy. A pre-treatment of LNCaP cells with IC50 concentrations of enzalutamide significantly sensitized them to radiotherapy through enhanced apoptosis. In contrast, enzalutamide resistant PC-3 cells were not sensitized to radiotherapy by androgen blockade. These results provide evidence that the enzalutamide/radiotherapy combination could maximize therapeutic responses in patients with enzalutamide-sensitive prostate cancer.

cancer biology↗
bioRxiv2018

Senescent CD4 T cells unequivocally identify primary resistance and risk of hyperprogression to PD-L1/PD-1 immune checkpoint blockade in lung cancer

The majority of lung cancer patients are refractory to PD-L1/PD-1 blockade monotherapy. This therapy may even accelerate progression and death in a group of patients called hyperprogressors. Here we demonstrate that the efficacy of PD-L1/PD-1 blockade therapy relies on baseline circulating highly-differentiated CD28- CD27- CD4 T cells (THD cells), which segregate patients in two non-overlapping groups. THD cells in cancer patients mostly comprised of central memory subsets that potently co-upregulated PD-1 and LAG3 upon antigen recognition. Low baseline THD numbers unequivocally identified intrinsic non-responders and hyperprogressors, whom aberrantly responded to therapy with a potent systemic proliferative THD cell burst. Responder patients showed significant reductions in systemic CD4 THD cells throughout therapy linked to expansion of the CD28+ CD27+ CD4 T cell compartment. Quantification of THD cells from peripheral blood samples prior to therapy allows identification of non-responders, hyperprogressors and responders, a critical issue in clinical oncology. These results place CD4 T cell responses at the center of anti-tumor immunity.

cancer biology↗