B cell profiles, antibody repertoire and reactivity reveal dysregulated responses with autoimmune features in melanoma.
B cell profiles, antibody repertoire and reactivity reveal dysregulated responses with autoimmune features in melanoma.
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DOI：
10.1038/s41467-023-39042-y
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发表时间：
2023-06-08
影响因子：
16.6
通讯作者：
Karagiannis, Sophia N.
中科院分区：
文献类型：
--
作者：
Crescioli, Silvia;Correa, Isabel;Ng, Joseph;Willsmore, Zena N.;Laddach, Roman;Chenoweth, Alicia;Chauhan, Jitesh;Di Meo, Ashley;Stewart, Alexander;Kalliolia, Eleni;Alberts, Elena;Adams, Rebecca;Harris, Robert J.;Mele, Silvia;Pellizzari, Giulia;Black, Anna B. M.;Bax, Heather J.;Cheung, Anthony;Nakamura, Mano;Hoffmann, Ricarda M.;Terranova-Barberio, Manuela;Ali, Niwa;Batruch, Ihor;Soosaipillai, Antoninus;Prassas, Ioannis;Ulndreaj, Antigona;Chatanaka, Miyo K.;Nuamah, Rosamund;Kannambath, Shichina;Dhami, Pawan;Geh, Jenny L. C.;Ross, Alastair D. MacKenzie;Healy, Ciaran;Grigoriadis, Anita;Kipling, David;Karagiannis, Panagiotis;Dunn-Walters, Deborah K.;Diamandis, Eleftherios P.;Tsoka, Sophia;Spicer, James;Lacy, Katie E.;Fraternali, Franca;Karagiannis, Sophia N.
众所周知，B细胞有助于抗肿瘤免疫反应，特别是在免疫原性肿瘤如黑色素瘤中，但在这些癌症中尚未详细描述体液免疫。在这里，我们展示了黑色素瘤患者循环和肿瘤驻留B细胞以及血清抗体样本的综合表型。与配对样本中的血液相比，记忆B细胞在肿瘤中富集，并具有与特定同种型相关的独特抗体库。肿瘤相关B细胞经历克隆扩增、类开关重组、体细胞超突变和受体修正。与血液相比，肿瘤相关B细胞产生的抗体具有比例较高的非生产性序列和明显的互补性，决定了3区特性。观察到的特征是亲和成熟和多反应性的迹象，表明肿瘤微环境中存在活跃和异常的自身免疫样反应。与此一致的是，肿瘤来源的抗体具有多反应性，并以自身抗原识别为特征。血清抗体显示出对自身免疫性疾病和癌症抗原的反应性，与切除后状态相比，活动性疾病患者的血清抗体水平更高。因此，我们的研究结果揭示了具有独特抗体库和特异性的B细胞谱系失调，以及具有自身免疫样特征的克隆扩增肿瘤浸润B细胞，形成了黑色素瘤的体液免疫反应。B细胞在黑色素瘤肿瘤免疫微环境的形成和抗肿瘤免疫应答中起着积极的作用。作者发现肿瘤内B细胞异常活化，产生潜在的自身反应性抗体。
B cells are known to contribute to the anti-tumor immune response, especially in immunogenic tumors such as melanoma, yet humoral immunity has not been characterized in these cancers to detail. Here we show comprehensive phenotyping in samples of circulating and tumor-resident B cells as well as serum antibodies in melanoma patients. Memory B cells are enriched in tumors compared to blood in paired samples and feature distinct antibody repertoires, linked to specific isotypes. Tumor-associated B cells undergo clonal expansion, class switch recombination, somatic hypermutation and receptor revision. Compared with blood, tumor-associated B cells produce antibodies with proportionally higher levels of unproductive sequences and distinct complementarity determining region 3 properties. The observed features are signs of affinity maturation and polyreactivity and suggest an active and aberrant autoimmune-like reaction in the tumor microenvironment. Consistent with this, tumor-derived antibodies are polyreactive and characterized by autoantigen recognition. Serum antibodies show reactivity to antigens attributed to autoimmune diseases and cancer, and their levels are higher in patients with active disease compared to post-resection state. Our findings thus reveal B cell lineage dysregulation with distinct antibody repertoire and specificity, alongside clonally-expanded tumor-infiltrating B cells with autoimmune-like features, shaping the humoral immune response in melanoma. B cells are playing an active role in shaping the tumour immune microenvironment and the anti-tumour immune response in melanomas. Here authors show that intra-tumoral B cells are aberrantly activated and produce antibodies that are potentially autoreactive.
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影响因子：
46.9
作者：
Bolotin DA;Poslavsky S;Davydov AN;Frenkel FE;Fanchi L;Zolotareva OI;Hemmers S;Putintseva EV;Obraztsova AS;Shugay M;Ataullakhanov RI;Rudensky AY;Schumacher TN;Chudakov DM
通讯作者：
Chudakov DM
影响因子：
7.2
作者：
Chiaruttini G;Mele S;Opzoomer J;Crescioli S;Ilieva KM;Lacy KE;Karagiannis SN
通讯作者：
Karagiannis SN
影响因子：
4.4
作者：
Edwards, MR;Brouwer, W;Collins, AM
通讯作者：
Collins, AM
影响因子：
64.8
作者：
Cabrita, Rita;Lauss, Martin;Jonsson, Goran
通讯作者：
Jonsson, Goran
影响因子：
--
作者：
Giudicelli, Veronique;Brochet, Xavier;Lefranc, Marie-Paule
通讯作者：
Lefranc, Marie-Paule