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Review
. 2015 Apr;15(4):201-15.
doi: 10.1038/nrc3907. Epub 2015 Mar 19.

Haematological malignancies: at the forefront of immunotherapeutic innovation

Pavan Bachireddy  1 , Ute E Burkhardt  2 , Mohini Rajasagi  3 , Catherine J Wu  1
Affiliations
Review

Haematological malignancies: at the forefront of immunotherapeutic innovation

Pavan Bachireddy et al. Nat Rev Cancer. 2015 Apr.

Abstract

The recent successes of cancer immunotherapies have stimulated interest in the potential widespread application of these approaches; haematological malignancies have provided both initial proofs of concept and an informative testing ground for various immune-based therapeutics. The immune-cell origin of many of the blood malignancies provides a unique opportunity both to understand the mechanisms of cancer immune responsiveness and immune evasion, and to exploit these mechanisms for therapeutic purposes.

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Figures

Figure 1
Figure 1. Strategies of co-opting physiologic immune programs
This figure summarizes the mechanisms observed in blood cancers of hijacking the physiologic circuitry of their normal counterparts (left column) to drive tumor growth and manipulate endogenous immune responses (right column). Example malignancies are listed centrally for each mechanism (row). A, on the left panel, illustrates an IL-7-mediated signaling pathway that drives physiologic homeostatic proliferation of T cells. In contrast, the right-sided panel shows that, by acquiring somatic mutations throughout this pathway (indicated by black color), blood cancers such as T-ALL can drive autonomous signaling. B highlights a similar phenomenon via the BCR signalling pathway that is activated by multiple B cell malignancies through acquired somatic mutations of the BCR itself as well as downstream components (indicated by black color). C depicts the typical antigen-specific activation of T cells mediated by professional antigen presenting cells (APCs) in the physiologic setting (left); in contrast, the lack of co-stimulation during antigen (Ag) presentation by malignant cells can induce T cell anergy (right). In D, the conventional role of HMGB1 as a “danger” signal emitted by dying cancer cells that stimulates and attracts anti-tumor T cells (left panel) is reversed in CLL in which (right panel) HMGB1 may promote differentiation of monocytes into nurse-like cells (NLCs) to promote CLL cell survival in vivo. Finally, E portrays the duality of Th1-led inflammation, with the left panel attributing tumor-destructive roles to CD8+ T cells and macrophages and tumor-promoting activities to regulatory T cells (Tregs); the right panel ascribes tumor-survival signals to CD4+ Th1 cells and a potential anti-tumor influence to Tregs as seen in CLL, cHL, FL and MM.
Figure 2
Figure 2. Timeline of major immunotherapeutic advances within hematologic malignancies
The figure depicts four areas of potential vulnerability in the tumor-immune relationship and the historical development of corresponding immune therapies. 1 emphasizes the potency of immunologic targeting of tumor surface antigens, primarily illustrated through mAbs. 2 highlights the long-standing influence of boosting immune effectors on immune therapy via DLI and now encapsulated by CAR-T cells. 3 recognizes the importance of activating tumor antigen-specific immunity. 4 underscores the potency of overcoming inhibitory immune suppression in the tumor microenvironment. BTD, US FDA’s breakthrough therapy designation; R/R, relapsed/refractory; CTL, cytotoxic T lymphocyte; ASCT, autologous stem cell transplantation.
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References

    1. Pardoll DM. The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer. 2012;12:252–64. A good review of immune checkpoints, particularly CTLA-4 and PD-1, within cancer immunotherapy. - PMC - PubMed
    1. Gattiker HH, Wiltshaw E, Galton DA. Spontaneous regression in non-Hodgkin’s lymphoma. Cancer. 1980;45:2627–32. - PubMed
    1. Del Giudice I, et al. Spontaneous regression of chronic lymphocytic leukemia: clinical and biologic features of 9 cases. Blood. 2009;114:638–46. - PubMed
    1. Nadler LM, et al. A unique cell surface antigen identifying lymphoid malignancies of B cell origin. J Clin Invest. 1981;67:134–40. - PMC - PubMed
    1. Feuerer M, et al. Bone marrow as a priming site for T-cell responses to blood-borne antigen. Nat Med. 2003;9:1151–7. - PubMed

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