Local and systemic immune profiles of human pancreatic ductal adenocarcinoma revealed by single-cell mass cytometry.
Local and systemic immune profiles of human pancreatic ductal adenocarcinoma revealed by single-cell mass cytometry.
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用单细胞质量细胞术研究人胰腺导管腺癌的局部和全身免疫状态。
DOI：
10.1136/jitc-2022-004638
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发表时间：
2022-07
影响因子：
10.9
通讯作者：
中科院分区：
文献类型：
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作者：
胰腺导管腺癌（PDAC）是一种高度致命的恶性肿瘤，需要有效的（免疫）治疗策略。为了优化癌症免疫疗法的应用和开发，需要全面了解PDAC患者的局部和全身免疫特征。在这里，我们的目标是破译局部和全身免疫谱之间的相互作用，在治疗初治的PDAC患者。通过单细胞质量细胞术测量41种免疫细胞标志物，评估了11例PDAC患者的PDAC、匹配的非恶性胰腺组织、区域淋巴结、脾脏、门静脉血和外周血样本（手术前后收集）的免疫组成。此外，通过流式细胞术研究了肿瘤浸润性淋巴细胞的活化潜力，所述活化潜力由其产生细胞因子的能力确定。此外，通过多光谱免疫荧光证实了肿瘤微环境中肿瘤浸润的先天淋巴细胞的空间定位。我们发现，具有细胞毒性潜力的CD 103 + CD 8 + T细胞在PDAC免疫微环境中并不常见，并且缺乏活化标志物和检查点阻断分子程序性细胞死亡蛋白-1（PD-1）的表达。相反，与非恶性胰腺组织相比，PDAC组织显示B细胞和调节性T细胞的相对频率显著增加。此外，在PDAC组织中发现了以前未被认识的先天性淋巴细胞（ILC）群体（CD 127-CD 103 + CD 39 + CD 45 RO + ILC 1-like）。引人注目的是，胰腺癌样品中B细胞和调节性T细胞的相对频率增加反映在匹配的门静脉血液样品中，而不是在外周血中，表明浸润PDAC微环境的免疫细胞的区域富集。手术后，外周血中髓样树突状细胞的频率降低。我们的工作证明了PDAC组织中的免疫抑制景观，通常被剥夺了细胞毒性T细胞，并富含调节性T细胞和B细胞。PDAC中ILC 1样细胞的抗肿瘤潜力可用于治疗。重要的是，从门静脉分离的血液中检测到的免疫谱反映了PDAC微环境的免疫细胞组成，表明该解剖位置可能是肿瘤相关免疫细胞亚群的来源。
Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy in need of effective (immuno)therapeutic treatment strategies. For the optimal application and development of cancer immunotherapies, a comprehensive understanding of local and systemic immune profiles in patients with PDAC is required. Here, our goal was to decipher the interplay between local and systemic immune profiles in treatment-naïve patients with PDAC. The immune composition of PDAC, matched non-malignant pancreatic tissue, regional lymph nodes, spleen, portal vein blood, and peripheral blood samples (collected before and after surgery) from 11 patients with PDAC was assessed by measuring 41 immune cell markers by single-cell mass cytometry. Furthermore, the activation potential of tumor-infiltrating lymphocytes as determined by their ability to produce cytokines was investigated by flow cytometry. In addition, the spatial localization of tumor-infiltrating innate lymphocytes in the tumor microenvironment was confirmed by multispectral immunofluorescence. We found that CD103+CD8+ T cells with cytotoxic potential are infrequent in the PDAC immune microenvironment and lack the expression of activation markers and checkpoint blockade molecule programmed cell death protein-1 (PD-1). In contrast, PDAC tissues showed a remarkable increased relative frequency of B cells and regulatory T cells as compared with non-malignant pancreatic tissues. Besides, a previously unappreciated innate lymphocyte cell (ILC) population (CD127–CD103+CD39+CD45RO+ ILC1-like) was discovered in PDAC tissues. Strikingly, the increased relative frequency of B cells and regulatory T cells in pancreatic cancer samples was reflected in matched portal vein blood samples but not in peripheral blood, suggesting a regional enrichment of immune cells that infiltrate the PDAC microenvironment. After surgery, decreased frequencies of myeloid dendritic cells were found in peripheral blood. Our work demonstrates an immunosuppressive landscape in PDAC tissues, generally deprived of cytotoxic T cells and enriched in regulatory T cells and B cells. The antitumor potential of ILC1-like cells in PDAC may be exploited in a therapeutic setting. Importantly, immune profiles detected in blood isolated from the portal vein reflected the immune cell composition of the PDAC microenvironment, suggesting that this anatomical location could be a source of tumor-associated immune cell subsets.
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影响因子：
28.2
作者：
Pylayeva-Gupta Y;Das S;Handler JS;Hajdu CH;Coffre M;Koralov SB;Bar-Sagi D
通讯作者：
Bar-Sagi D
影响因子：
12.3
作者：
McLaren W;Gil L;Hunt SE;Riat HS;Ritchie GR;Thormann A;Flicek P;Cunningham F
通讯作者：
Cunningham F
影响因子：
2.5
作者：
Pezzotti, N.;Hollt, T.;Vilanova, A.
通讯作者：
Vilanova, A.
DOI：
10.1158/1078-0432.ccr-18-1955
发表时间：
2019-04-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Bernard V;Semaan A;Huang J;San Lucas FA;Mulu FC;Stephens BM;Guerrero PA;Huang Y;Zhao J;Kamyabi N;Sen S;Scheet PA;Taniguchi CM;Kim MP;Tzeng CW;Katz MH;Singhi AD;Maitra A;Alvarez HA
通讯作者：
Alvarez HA
影响因子：
17.1
作者：
Gaudillière B;Fragiadakis GK;Bruggner RV;Nicolau M;Finck R;Tingle M;Silva J;Ganio EA;Yeh CG;Maloney WJ;Huddleston JI;Goodman SB;Davis MM;Bendall SC;Fantl WJ;Angst MS;Nolan GP
通讯作者：
Nolan GP