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Shaping of an effective immune microenvironment to and by cancer cells

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Abstract

A high density of intratumoral effector memory CD8+/Th1 T cells is associated with favorable prognosis in most cancers and may be induced or increased by immunotherapy. Efficient adaptive immune reactions are shaped in tumor adjacent tertiary lymphoid structures, which exhibit all characteristics of immunity generating lymphoid formations in reactive lymph nodes. Malignant tumor cells impact favorably or deleteriously their immune microenvironment if they bear genetic mutations that result in neo-antigens or by producing chemokines and cytokines that recruit lymphocytes and myeloid cells or increase inflammation and neo-angiogenesis. This intricate network of interactions results in control or escape of tumors, and its understanding will help define goals to monitor efficiency of immunotherapies.

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Abbreviations

AID:

Activation-induced cytidine deaminase

CAR:

Chimeric antigen receptor

CIN:

Cervical intraepithelial neoplasia

CT:

Core tumor

DC:

Dendritic cell

HPV:

Human papilloma virus

IM:

Invasive margin

MDSC:

Myeloid-derived suppressor cell

MSI:

Microsatellite instability

NSCLC:

Non-small cell lung cancer

OS:

Overall survival

PFS:

Progression-free survival

SLO:

Secondary lymphoid organ

Ti-BALT:

Tumor-induced bronchus-associated lymphoid tissue

TIL:

Tumor-infiltrating leukocyte

TLS:

Tertiary lymphoid structure

Treg cell:

Regulatory T cell

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Acknowledgments

We wish to thank Marco Alifano, Luc de Chaisemartin Diane Damotte, Samantha Knockaert, Laetitia Lacroix, Audrey Lupo, Hanane Ouakrim, Romain Remark and Pierre Validire for their active participation to the studies and Pierre Laurent-Puig, Aurelien de Reyniès, Benoit Beuselinck and Jessica Zucman-Rossi for their numerous and exciting discussions. This work was supported by Institut National de la Santé er 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 and Canceropole Ile de France (2011-1-PLBIO-06-INSERM 6-1, PLBIO09-088-IDF-KROEMER, 11LAXE62_9UMS872 FRIDMAN).

Conflict of interest

Wolf-Herman Fridman received honorarium from Laboratoire du Fractionnement et des Biotechnologies (LFB), Pierre Fabre Medicament and Sanofi. The other authors declare that they have no conflict of interest.

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Becht, E., Goc, J., Germain, C. et al. Shaping of an effective immune microenvironment to and by cancer cells. Cancer Immunol Immunother 63, 991–997 (2014). https://doi.org/10.1007/s00262-014-1590-3

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