Dendritic Cells in Tumor-Associated Tertiary Lymphoid Structures Signal a Th1 Cytotoxic Immune Contexture and License the Positive Prognostic Value of Infiltrating CD8+ T Cells

被引：528

作者：

Goc, Jeremy ^{[1
,2
,3
]}

Germain, Claire ^{[1
,2
,3
]}

Thi Kim Duy Vo-Bourgais ^{[1
,2
,3
]}

Lupo, Audrey ^{[1
,2
,3
,4
]}

Klein, Christophe ^{[1
,2
]}

Knockaert, Samantha ^{[1
,2
,3
]}

de Chaisemartin, Luc ^{[1
,2
,3
]}

Ouakrim, Hanane ^{[1
,2
,3
]}

Becht, Etienne ^{[1
,2
,3
]}

Alifano, Marco ^{[5
]}

Validire, Pierre ^{[1
,6
]}

Remark, Romain ^{[1
,2
,3
]}

Hammond, Scott A. ^{[8
]}

Cremer, Isabelle ^{[1
,2
,3
]}

Damotte, Diane ^{[1
,2
,3
,4
]}

Fridman, Wolf-Herman ^{[1
,2
,3
,7
]}

Sautes-Fridman, Catherine ^{[1
,2
,3
]}

Dieu-Nosjean, Marie-Caroline ^{[1
,2
,3
]}

机构：

[1] INSERM, Cordeliers Res Ctr, Lab ImmuneMicroenvironm & Tumors, U872, F-75270 Paris, France

[2] Univ Paris 06, Paris, France

[3] Univ Paris 05, UMRS 872, Paris, France

[4] Hop Hotel Dieu, AP HP, Dept Pathol, Paris, France

[5] Hop Hotel Dieu, AP HP, Dept Thorac Surg, Paris, France

[6] Inst Mutualiste Montsouris, Dept Pathol, Paris, France

[7] Hop Europeen Georges Pompidou, AP HP, Dept Immunol, Paris, France

[8] MedImmune LLC, Oncol Res, Gaithersburg, MD USA

来源：

CANCER RESEARCH | 2014年 / 74卷 / 03期

关键词：

HIGH ENDOTHELIAL VENULES; LUNG-CANCER; CUTANEOUS MELANOMA; OVARIAN-CANCER; BREAST-CANCER; LYMPHOCYTES; SURVIVAL; CLASSIFICATION; TRAFFICKING; NEOGENESIS;

D O I：

10.1158/0008-5472.CAN-13-1342

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

Tumor-infiltrating T cells, particularly CD45RO(+)CD8(+) memory T cells, confer a positive prognostic value in human cancers. However, the mechanisms that promote a protective T-cell response in the tumor microenvironment remain unclear. In chronic inflammatory settings such as the tumor microenvironment, lymphoid neogenesis can occur to create local lymph node-like structures known as tertiary lymphoid structures (TLS). These structures can exacerbate a local immune response, such that TLS formation in tumors may help promote an efficacious immune contexture. However, the role of TLS in tumors has yet to be investigated carefully. In lung tumors, mature dendritic cells ( DC) present in tumor-associated TLS can provide a specific marker of these structures. In this study, we evaluated the influence of TLS on the characteristics of the immune infiltrate in cohorts of prospective and retrospective human primary lung tumors (n = 458). We found that a high density of mature DC correlated closely to a strong infiltration of T cells that are predominantly of the effector-memory phenotype. Moreover, mature DC density correlated with expression of genes related to T-cell activation, T-helper 1 (Th1) phenotype, and cytotoxic orientation. Lastly, a high density of TLS-associated DC correlated with long-term survival, which also allowed a distinction of patients with high CD8(+) T-cell infiltration but a high risk of death. Taken together, our results show how tumors infiltrated by TLS-associated mature DC generate a specific immune contexture characterized by a strong Th1 and cytotoxic orientation that confers the lowest risk of death. Furthermore, our findings highlight the pivotal function of TLS in shaping the immune character of the tumor microenvironment, in promoting a protective immune response mediated by T cells against cancer. Cancer Res; 74(3); 705-15. (C)2013 AACR.

引用

页码：705 / 715

页数：11

共 46 条

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