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Emerging therapies provide new opportunities to reshape the multifaceted interactions between the immune system and lymphoma cells

Leukemia volume 30, pages 1805–1815 (2016)Cite this article

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Abstract

The acquisition of a complete neoplastic phenotype requires cancer cells to develop escape mechanisms from the host immune system. This phenomenon, commonly referred to as ‘immune evasion,’ represents a hallmark of cancers and results from a Darwinian selection of the fittest tumor clones. First reported in solid tumors, cancer immunoescape characterizes several hematological malignancies. The biological bases of cancer immunoescape have recently been disclosed and include: (i) impaired human leukocyte antigen-mediated cancer cell recognition (B2M, CD58, CTIIA, CD80/CD86, CD28 and CTLA-4 mutations); (ii) deranged apoptotic mechanisms (reduced pro-apoptotic signals and/or increased expression of anti-apoptotic molecules); and (iii) changes in the tumor microenvironment involving regulatory T cells and tumor-associated macrophages. These immune-escape mechanisms characterize both Hodgkin and non-Hodgkin (B and T cell) lymphomas and represent a promising target for new anti-tumor therapies. In the present review, the principles of cancer immunoescape and their role in human lymphomagenesis are illustrated. Current therapies targeting these pathways and possible applications for lymphoma treatment are also addressed.

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Acknowledgements

GI is supported by the Italian Association for Cancer Research (AIRC) (5x1000 No. 10007); ImmOnc (BIO F.E.S.R. 2007/13, Asse 1 ‘Ricerca e innovazione’ della LR 34/2004) the Oncology Program of Compagnia di San Paolo, Torino and Ricerca Finalizzata, Ministero della Salute. FB is supported by the Gelu Foundation (Switzerland). GI received research funds from Oncoethix. FB received research funds or advisory honoraria (for the institution) from Oncoethix, PIQUR Therapeutics AG, EMD Serono, Bayer AG, Sigma Tau, Italfarmaco, CTI Life Sciences and Celgene.

Author contributions

GI conceived the study and wrote the manuscript. MB, MP, FB and GI wrote the manuscript.

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Author notes

  1. M Pizzi and M Boi: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY, USA

    M Pizzi, M Boi & G Inghirami

  2. Department of Medicine-DIMED, General Pathology and Cytopathology Unit, University of Padua, Padua, Italy

    M Pizzi

  3. Lymphoma and Genomics Research Program, IOR Institute of Oncology Research, Bellinzona, Switzerland

    F Bertoni

  4. IOSI Oncology Institute of Southern Switzerland, Bellinzona, Switzerland

    F Bertoni

  5. Department of Molecular Biotechnology and Health Science and Center for Experimental Research and Medical Studies (CeRMS), University of Turin, Turin, Italy

    G Inghirami

  6. Department of Pathology and NYU Cancer Center, New York University School of Medicine, New York, NY, USA

    G Inghirami

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Correspondence to G Inghirami.

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Pizzi, M., Boi, M., Bertoni, F. et al. Emerging therapies provide new opportunities to reshape the multifaceted interactions between the immune system and lymphoma cells. Leukemia 30, 1805–1815 (2016). https://doi.org/10.1038/leu.2016.161

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