We are analyzing https://link.springer.com/article/10.1007/s00262-013-1396-8.

Title:
Therapeutic regulation of myeloid-derived suppressor cells and immune response to cancer vaccine in patients with extensive stage small cell lung cancer | Cancer Immunology, Immunotherapy
Description:
Myeloid-derived suppressor cells (MDSC) are one of the major factors limiting the efficacy of immune therapy. In a clinical trial of patients with extensive stage small cell lung cancer (SCLC), we tested the possibility that targeting MDSC can improve the induction of immune responses by a cancer vaccine. Forty-one patients with extensive stage SCLC were randomized into three arms: arm A—control, arm B—vaccination with dendritic cells transduced with wild-type p53, and arm C—vaccination in combination with MDSC targeted therapy with all-trans-retinoic acid (ATRA). Interim results of the ongoing clinical trial are presented. Pre-treatment levels of MDSC populations in patients from all three arms were similar. Vaccine alone did not affect the proportion of MDSC, whereas in patients treated with ATRA, the MDSC decreased more than twofold (p = 0.02). Before the start of treatment, no patients had detectable p53-specific responses in IFN-γ ELISPOT. Sequential measurements did not show positive p53 responses in any of the 14 patients from arm A. After immunization, only 3 out of 15 patients (20 %) from arm B developed a p53-specific response (p = 0.22). In contrast, in arm C, 5 out of 12 patients (41.7 %) had detectable p53 responses (p = 0.012). The proportion of granzyme B-positive CD8+ T cells was increased only in patients from arm C but not in arm B. Depletion of MDSC substantially improved the immune response to vaccination, suggesting that this approach can be used to enhance the effect of immune interventions in cancer.
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Topics {✒️}

dung-tsa chen & dmitry gabrilovich interferon-gamma-producing t-cells small-cell lung cancer myeloid-derived suppressor cells month download article/chapter immature gr-1 + myeloid cells functional antigen-presenting cells trans-retinoic acid treatment myeloid cell-mediated immunosuppression granzyme b-positive cd8+ inhibitory b7-family molecules il-1alpha vaccine depends myeloid suppressor cells immature myeloid cells wild-type p53 single-dose cyclophosphamide associates trans-retinoic acid detectable p53-specific responses diaz-montero cm full article pdf article cancer immunology extensive stage sclc cell therapy core clinical cancer stage related subjects p53 cancer vaccine dendritic cells transduced colony-stimulating factors privacy choices/manage cookies p53-specific response cancer vaccine ima901 lung cancer 40 affecting th17 cells detectable p53 responses tumour microenvironment metastatic tumor burden fusion protein vaccine multipeptide immune response improves immune response authors cristina iclozan myeloid cells tumor-induced tolerance interleukin-12-secreting dendritic cell response il-1ri availability article iclozan check access instant access ongoing clinical trial pdf+html kotsakis

Questions {❓}

Wieand HS (2005) Randomized phase II trials: what does randomization gain?

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