Kandalaft, L.E. (Lana E.)

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2019 - 20202

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    Quantitative and qualitative impairments in dendritic cell subsets of patients with ovarian or prostate cancer
    (Elsevier, 2020) Monique-de-Vries, I.J. (Ingrid Jolanda); Mastelic-Gavillet, B. (Beatris); Kandalaft, L.E. (Lana E.); Vigano, S. (Selena); Coukos, G. (George); Jichlinski, P. (Patrice); Lozano, L.E. (Leyder Elena); Derre, L. (Laurent); Harari, A. (Alexandre); Romero, P.J. (Pedro J.); Dartiguenave, F. (Florence); Inoges, S. (Susana); Melero, I. (Ignacio); Wyss, T. (Tania); Sarivalasis, A. (Apostolos)
    Background Dendritic cells (DCs) are the most efficient antigen-presenting cells, hence initiating a potent and cancer-specific immune response. This ability (mainly using monocyte-derived DCs) has been exploited in vaccination strategies for decades with limited clinical efficacy. Another alternative would be the use of conventional DCs (cDCs) of which at least three subsets circulate in human blood: cDC1s (CD141bright), cDC2s (CD1c+) and plasmacytoid DCs. Despite their paucity, technical advances may allow for their selection and clinical use. However, many assumptions concerning the DC subset biology depend on observations from mouse models, hindering their translational potential. In this study, we characterise human DCs in patients with ovarian cancer (OvC) or prostate cancer (PrC). Patients and methods Whole blood samples from patients with OvC or PrC and healthy donors (HDs) were evaluated by flow cytometry for the phenotypic and functional characterisation of DC subsets. Results In both patient groups, the frequency of total CD141+ DCs was lower than that in HDs, but the cDC1 subset was only reduced in patients with OvC. CD141+ DCs showed a reduced response to the TLR3 agonist poly (I:C) in both groups of patients. An inverse correlation between the frequency of cDC1s and CA125, the OvC tumour burden marker, was observed. Consistently, high expression of CLEC9A in OvC tissue (The Cancer Genome Atlas data set) indicated a better overall survival. Conclusions cDC1s are reduced in patients with OvC, and CD141+ DCs are quantitatively and qualitatively impaired in patients with OvC or PrC. CD141+ DC activation may predict functional impairment. The loss of cDC1s may be a bad prognostic factor for patients with OvC.
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    The clinical application of cancer immunotherapy based on naturally circulating dendritic cells
    (BMJ, 2019) Dzionek, A. (Andrzej); Kandalaft, L.E. (Lana E.); Sancho, D. (David); Coukos, G. (George); Wculek, S.K. (Stefanie K.); Romero, P.J. (Pedro J.); Schwarze, J.K. (Julia Katharina); Schreibelt, G. (Gerty); Vries, J. (Jolanda) de; Neyns, B. (Bart); Melero, I. (Ignacio); Rabold, K. (Katrin); Bol, K.F. (Kalijn F.); Teijeira, A. (Álvaro)
    Dendritic cells (DCs) can initiate and direct adaptive immune responses. This ability is exploitable in DC vaccination strategies, in which DCs are educated ex vivo to present tumor antigens and are administered into the patient with the aim to induce a tumor-specific immune response. DC vaccination remains a promising approach with the potential to further improve cancer immunotherapy with little or no evidence of treatment-limiting toxicity. However, evidence for objective clinical antitumor activity of DC vaccination is currently limited, hampering the clinical implementation. One possible explanation for this is that the most commonly used monocyte-derived DCs may not be the best source for DC-based immunotherapy. The novel approach to use naturally circulating DCs may be an attractive alternative. In contrast to monocyte-derived DCs, naturally circulating DCs are relatively scarce but do not require extensive culture periods. Thereby, their functional capabilities are preserved, the reproducibility of clinical applications is increased, and the cells are not dysfunctional before injection. In human blood, at least three DC subsets can be distinguished, plasmacytoid DCs, CD141+ and CD1c+ myeloid/conventional DCs, each with distinct functional characteristics. In completed clinical trials, either CD1c+ myeloid DCs or plasmacytoid DCs were administered and showed encouraging immunological and clinical outcomes. Currently, also the combination of CD1c+ myeloid and plasmacytoid DCs as well as the intratumoral use of CD1c+ myeloid DCs is under investigation in the clinic. Isolation and culture strategies for CD141+ myeloid DCs are being developed. Here, we summarize and discuss recent clinical developments and future prospects of natural DC-based immunotherapy.