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

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Defects in T Cell Trafficking and Resistance to Cancer Immunotherapy

Part of the book series: Resistance to Targeted Anti-Cancer Therapeutics ((RTACT,volume 9))

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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.

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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

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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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  1. Lyon University, Lyon, France

    Bertrand Dubois, Coline Couillault & Christophe Caux

  2. INSERM U1052 CNRS UMR5286, Centre de Recherche en Cancérologie de Lyon, Lyon, France

    Bertrand Dubois, Coline Couillault & Christophe Caux

  3. Laboratory “Cancer, Immune Control, and Escape”, INSERM UMRS1138, Cordeliers Research Center, 15, rue de l’Ecole de Médecine, F-75270, Paris, Cedex 06, France

    Hélène Kaplon & Marie-Caroline Dieu-Nosjean

  4. Sorbonne University, Pierre and Marie Curie University, UMRS1138, Paris, France

    Hélène Kaplon & Marie-Caroline Dieu-Nosjean

  5. Sorbonne Paris Cité University, Paris Descartes University, UMRS1138, Paris, France

    Hélène Kaplon & Marie-Caroline Dieu-Nosjean

  6. Centre Léon Bérard, Lyon, France

    Christophe Caux

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  1. Bertrand Dubois
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Correspondence to Marie-Caroline Dieu-Nosjean .

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  1. Institut Cochin INSERM, Université Paris Descartes, Paris, France

    Emmanuel Donnadieu

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Dubois, B., Kaplon, H., Couillault, C., Caux, C., Dieu-Nosjean, MC. (2016). Cancer-Associated Tertiary Lymphoid Structures, from Basic Knowledge Toward Therapeutic Target in Clinic. In: Donnadieu, E. (eds) Defects in T Cell Trafficking and Resistance to Cancer Immunotherapy. Resistance to Targeted Anti-Cancer Therapeutics, vol 9. Springer, Cham. https://doi.org/10.1007/978-3-319-42223-7_5

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