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Immune Infiltration in Human Cancer: Prognostic Significance and Disease Control

  • Wolf H. Fridman
  • Jérome Galon
  • Marie-Caroline Dieu-Nosjean
  • Isabelle Cremer
  • Sylvain Fisson
  • Diane Damotte
  • Franck Pagès
  • Eric Tartour
  • Catherine Sautès-Fridman
Chapter
Part of the Current Topics in Microbiology and Immunology book series (CT MICROBIOLOGY, volume 344)

Abstract

The interplay between tumors and their immunologic microenvironment is complex and difficult to decipher, but its understanding is of seminal importance for the development of novel prognostic markers and therapeutic strategies. This chapter discusses tumor−immune interactions in several human cancers that illustrate various aspects of this complexity and proposes an integrated scheme of the impact of local immune reactions on clinical outcome. Thus, the fact that a strong infiltration of memory T cells with a Th1 and cytotoxic pattern is the strongest predictor for recurrence and metastasis is exemplified in colorectal cancer in which intratumoral chemokines shape an efficient immune reaction. Based on these data, we propose an immune score that predicts recurrence in early stage (UICC-TNM stage I-II) cancers. Studies on non-small lung cancers have confirmed findings of colorectal cancers and have addressed the question of the sites where antitumor immune reactions may take place. Tertiary lymphoid structures (TLS) adjacent to the tumor nest are sites of intense activity with mature dendritic cells in contact with T cells and germinal-like centers with proliferating B cells. The large number of these TLS being correlated with disease specific and overall survival tempts to postulate that they are privileged sites to mount an efficient antitumor reaction. Inflammation is a major component of human tumors and chronic inflammation is generally of bad prognosis. Head and neck cancers are highly inflammatory and two ways to modulate inflammation in these diseases are presented here: soluble IL-15 receptor α (IL-15 Rα) increases the pro-inflammatory effect of IL-15 and aggravates inflammation resulting in poor prognosis when found at high levels in the plasma of patients. By contrast, infiltration of regulatory T cells is paradoxically beneficial for local control of head and neck tumors, probably by “cooling down” the inflammatory process. The modulation of other aspects of innate immunity may also result in paradoxical effects such as the signaling through Toll like receptors 7 and 8 expressed on lung tumor cells which induce an aggressive tumoral phenotype. Finally, the analysis of primary intraocular lymphoma, which develops in the eye, exemplifies the induction of an antitumor immune reaction in an “immune sanctuary,” presenting all the complexities of the tumor–immune interplay in “open” tissues such as the colon or the lung.

Keywords

Overall Survival Mature Dendritic Cell Human Papilloma Virus Invasive Margin Efficient Immune Reaction 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgments

This work was supported by grants from Association pour la Recherche sur le Cancer (ARC), National Cancer Institute (INCa), Canceropole Ile de France, Ville de Paris, Inserm, European Union (7FP, Geninca Consortium grant number 202230), Laboratoire Français de fractionnement et des Biotechnologies (LFB), and Pôle de Compétitivité Ile de France (Immucan). The authors wholeheartedly thank the doctoral and postdoctoral fellows, as well as the engineers and colleagues who performed the biological and statistical experiments: C. Badoual, G. Bindea, M. Camus, J. Cherfils, C. Daussy, L. de Chaisemartin, N. El Houda Afneznay, A. Gey, A. Kirilovski, C. Lagorce, L. Laurans, F. Marliot, B. Mlecnik, R. Molidor, F. Sandoval, M. Tosolini, V. Touitou, and Z. Trajanovski. They acknowledge the trustfull and enthusiastic collaboration with devoted and interactive clinicians and pathologists:M. Antoine, A. Berger, B. Bodaghi, D. Brasnu, P. Bruneval, J. Cadranel, N. Cassou, C. Danel, S. Hans, P. Le Hoang, H. Merle Béral, S. Oudart, P. Validire, P. Wind, and F. Zinzindouhé.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2010

Authors and Affiliations

  • Wolf H. Fridman
    • 1
    • 2
    • 3
    • 4
    • 5
  • Jérome Galon
    • 1
    • 2
    • 3
  • Marie-Caroline Dieu-Nosjean
    • 1
    • 2
    • 3
  • Isabelle Cremer
    • 1
    • 2
    • 3
  • Sylvain Fisson
    • 1
    • 2
    • 3
  • Diane Damotte
    • 1
    • 2
    • 3
  • Franck Pagès
    • 1
    • 2
    • 3
    • 4
    • 5
  • Eric Tartour
    • 4
    • 5
  • Catherine Sautès-Fridman
    • 1
    • 2
    • 3
  1. 1.INSERM U872Centre de Recherche des CordeliersParisFrance
  2. 2.UMRS 872Université Pierre et Marie Curie–Paris 6ParisFrance
  3. 3.UMRS 872Université Paris DescartesParisFrance
  4. 4.Service d’Immunologie BiologiqueHôpital Européen Georges Pompidou, AP-HPParisFrance
  5. 5.INSERM U872Centre de Recherche des CordeliersParisFrance

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