Sosa Cuevas Eleonora, Bendriss-Vermare Nathalie, Mouret Stephane, De Fraipont Florence, Charles Julie, Valladeau-Guilemond Jenny, Chaperot Laurence, Aspord Caroline
Institute for Advanced Biosciences, Immunobiology and Immunotherapy in Chronic Diseases Inserm U 1209 CNRS UMR 5309 Université Grenoble Alpes Grenoble France.
Etablissement Français du Sang Auvergne-Rhône-Alpes R&D Laboratory Grenoble France.
Clin Transl Immunology. 2022 May 3;11(5):e1382. doi: 10.1002/cti2.1382. eCollection 2022.
Plasmacytoid DCs (pDCs) play a critical yet enigmatic role in antitumor immunity through their pleiotropic immunomodulatory functions. Despite proof of pDC diversity in several physiological or pathological contexts, pDCs have been studied as a whole population so far in cancer. The assessment of individual pDC subsets is needed to fully grasp their involvement in cancer immunity, especially in melanoma where pDC subsets are largely unknown and remain to be uncovered.
We explored for the first time the features of diverse circulating and tumor-infiltrating pDC subsets in melanoma patients using multi-parametric flow cytometry, and assessed their clinical relevance. Based on CD80, PDL1, CD2, LAG3 and Axl markers, we provided an integrated overview of the frequency, basal activation status and functional features of pDC subsets in melanoma patients together with their relationship to clinical outcome.
Strikingly, we demonstrated that P3-pDCs (CD80PDL1) accumulated within the tumor of melanoma patients and negatively correlated with clinical outcomes. The basal activation status, diversification towards P1-/P2-/P3-pDCs and functionality of several pDC subsets upon TLR7/TLR9 triggering were perturbed in melanoma patients, and were differentially linked to clinical outcome.
Our study shed light for the first time on the phenotypic and functional heterogeneity of pDCs in the blood and tumor of melanoma patients and their potential involvement in shaping clinical outcomes. Such novelty brightens our understanding of pDC complexity, and prompts the further deciphering of pDCs' features to better apprehend and exploit these potent immune players. It highlights the importance of considering pDC diversity when developing pDC-based therapeutic strategies to ensure optimal clinical success.
浆细胞样树突状细胞（pDC）通过其多效性免疫调节功能在抗肿瘤免疫中发挥关键但尚不明确的作用。尽管在多种生理或病理情况下已证明pDC具有多样性，但迄今为止在癌症研究中一直将pDC作为一个整体群体进行研究。需要评估单个pDC亚群，以全面了解它们在癌症免疫中的作用，尤其是在黑色素瘤中，pDC亚群在很大程度上未知且有待发现。
我们首次使用多参数流式细胞术探索了黑色素瘤患者中不同循环和肿瘤浸润pDC亚群的特征，并评估了它们的临床相关性。基于CD80、PDL1、CD2、LAG3和Axl标记，我们提供了黑色素瘤患者中pDC亚群的频率、基础激活状态和功能特征的综合概述，以及它们与临床结果的关系。
令人惊讶的是，我们证明P3-pDC（CD80 PDL1）在黑色素瘤患者的肿瘤内积聚，并且与临床结果呈负相关。黑色素瘤患者中，TLR7/TLR9触发后几个pDC亚群的基础激活状态、向P1-/P2-/P3-pDC的分化以及功能受到干扰，并且与临床结果存在差异关联。
我们的研究首次揭示了黑色素瘤患者血液和肿瘤中pDC的表型和功能异质性，以及它们在塑造临床结果中的潜在作用。这一新颖发现加深了我们对pDC复杂性的理解，并促使进一步解读pDC的特征，以便更好地理解和利用这些强大的免疫细胞。它强调了在制定基于pDC的治疗策略时考虑pDC多样性以确保最佳临床疗效的重要性。
