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Cancer-Associated Tertiary Lymphoid Structures, from Basic Knowledge Toward Therapeutic Target in Clinic

  • Bertrand Dubois
  • Hélène Kaplon
  • Coline Couillault
  • Christophe Caux
  • Marie-Caroline Dieu-NosjeanEmail author
Chapter
Part of the Resistance to Targeted Anti-Cancer Therapeutics book series (RTACT, volume 9)

Abstract

The tumor growth is under the control of the immune system, and this represents a significant challenge for the development of new therapeutic strategies. It is now recognized that not only the density, but also the organization of tumor-infiltrating immune cells is critical for the shaping of the tumor microenvironment. In human cancers, several levels of structuration of lymphoid aggregates have been observed, including Tertiary Lymphoid Structures (TLS) displaying strong similarities with secondary lymphoid organs. In this review, we discuss about the role of immune cells homing selectively in the T-cell or B-cell zone of TLS with putative consequences on the initiation of efficient cellular and humoral immune responses against tumor, and ultimately on the clinical outcome of cancer patients. However, immunoregulatory cells may also infiltrate TLS and it is thus crucial to determine the circumstances in which TLS might be a site for the development of a suppressive and detrimental immune responses. We also discuss how TLS could be a useful marker of efficient immunotherapy, and raise the question of the capacity of immune-based vaccinations along with immune checkpoint blockade to induce TLS neogenesis. As TLS may represent the best place to induce or amplify protective immunity targeting neoantigens, TLS may be a promising target in order to boost anti-tumoral immunity in cancer patients.

Keywords

Tumor microenvironment Tertiary lymphoid structure Dendritic cell T cell Antibody Immune checkpoint Biomarker Immunointervention High endothelial venule Neoantigen 

Abbreviations

Ab

Antibody

ADCC

Antibody-Dependent Cell-mediated Cytotoxicity

Ag

Antigen

AID

Activation-Induced cytidine Deaminase

APC

Antigen-Presenting Cell

BCR

B-Cell Receptor

ccRCC

Clear cell Renal Cell Carcinoma

CDC

Complement-Dependent Cytotoxicity

CIN

Cervical Intraepithelial Neoplasia

CRC

Colorectal Cancer

CSR

Class Switch Recombination

CTL

Cytotoxic T lymphocyte

DC

Dendritic Cell

FcR

Fc Receptor

FcRn

Neonatal Fc Receptor

GALT

Gut-Associated Lymphoid Tissue

GC

Germinal Center

G-VAX

GM-CSF transfected tumor cell vaccine

GM-CSF

Granulocyte Macrophage Colony-Stimulating Factor

HCV

Hepatitis C Virus

HEV

High Endothelial Venule

HPV

Human Papilloma Virus

ICP

Immune CheckPoint

Ig

Immunoglobulin

LN

Lymph Node

MHC

Major Histocompatibility Complex

NK

Natural Killer cell

NSCLC

Non-Small Cell Lung Cancer

PAP

Prostate Acid Phosphatase

PB

Plasmablast

PC

Plasma Cell

PDAC

Pancreatic Ductal Adenocarcinoma

RCC

Renal Cell Carcinoma

SCC

Squamous Cell Carcinoma

SHM

Somatic HyperMutation

SLO

Secondary Lymphoid Organ

TAA

Tumor-Associated Antigen

TCM

Central-Memory T cell

TCR

T-Cell Receptor

TEM

Effector-memory T cell

TFH

Follicular Helper T cell

TLS

Tertiary Lymphoid Structure

TReg

Regulatory T cell

Notes

Acknowledgments

We wish to acknowledge the participation of members of the laboratories among whom Prs. C. Sautès-Fridman and W. H. Fridman, clinicians, and pathologists who participated in the articles referenced in our review.

Conflict statement: No potential conflicts of interest were disclosed.

Grants: This work was supported by Institut National de la Santé et de la Recherche Médicale (INSERM), University Paris Descartes, University Pierre et Marie Curie, SIRIC Cancer Research and Personalized Medicine (CARPEM), the LabeX Immuno-Oncology, Institut National du Cancer (INCa) and Canceropôle Ile-de-France, Fondation ARC pour la Recherche sur le Cancer, MedImmune, the LABEX DEVWECAN (ANR-10-LABX-0061) of University of Lyon, the program “Investissements d’Avenir” (ANR-11-IDEX-0007) operated by the French National Research Agency (ANR), and the SIRIC project (LYRIC, Grant No. INCa-4664). Hélène Kaplon was supported by a grant from La Ligue contre le Cancer.

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Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  • Bertrand Dubois
    • 1
    • 2
  • Hélène Kaplon
    • 3
    • 4
    • 5
  • Coline Couillault
    • 1
    • 2
  • Christophe Caux
    • 1
    • 2
    • 6
  • Marie-Caroline Dieu-Nosjean
    • 3
    • 4
    • 5
    Email author
  1. 1.Lyon UniversityLyonFrance
  2. 2.INSERM U1052 CNRS UMR5286, Centre de Recherche en Cancérologie de LyonLyonFrance
  3. 3.Laboratory “Cancer, Immune Control, and Escape”, INSERM UMRS1138, Cordeliers Research CenterParisFrance
  4. 4.Sorbonne University, Pierre and Marie Curie University, UMRS1138ParisFrance
  5. 5.Sorbonne Paris Cité University, Paris Descartes University, UMRS1138ParisFrance
  6. 6.Centre Léon BérardLyonFrance

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