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Advances and perspectives of dendritic cell-based active immunotherapies in follicular lymphoma

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Abstract

Follicular lymphoma (FL) is a remarkably immune-responsive malignancy, which is still considered incurable. As, standard immunochemotherapy is complex, toxic and not curative, improvement in FL care is now a crucial topic in hemato-oncology. Recently, we and others have shown that dendritic cell (DC)-based therapies allow a specific immune response associated with sustained lymphoma regression in a proportion of low-tumor burden FL patients. Importantly, the rate of objective clinical response (33–50%) and of sustained remission is remarkably higher compared to similar studies in solid tumors, corroborating the assumption of the immune responsiveness of FL. Our experimental intra-tumoral strategy combined injection with rituximab and interferon-α-derived dendritic cells (IFN-DC), a novel DC population particularly efficient in biasing T-helper response toward the Th1 type and in the cross-priming of CD8 + T cells. Noteworthy, intra-tumoral injection of DC is a new therapeutic option based on the assumption that following the induction of cancer-cell immunogenic death, unloaded DC would phagocytize in vivo the tumor associated antigens and give rise to a specific immune response. This approach allows the design of easy and inexpensive schedules. On the other hand, advanced and straightforward methods to produce clinical-grade antigenic formulations are currently under development. Both unloaded DC strategies and DC-vaccines are suited for combination with radiotherapy, immune checkpoint inhibitors, immunomodulators and metronomic chemotherapy. In fact, studies in animal models have already shown impressive results, while early-phase combination trials are ongoing. Here, we summarize the recent advances and the future perspectives of DC-based therapies in the treatment of FL patients.

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Abbreviations

DC:

Dendritic cells

FL:

Follicular lymphoma

GM-CSF:

Granulocyte macrophage colony-stimulating factor

ICI:

Immune checkpoint inhibitor

IFN-DC:

IFN-α-conditioned dendritic cells

IFN-α:

Interferon alpha

IFN-γ:

Interferon gamma

IL-4-DC:

Interleukine-4

KLH:

Keyhole limpet hemocyanin

LTB:

Low tumor burden

NHL:

Non-Hodgkin lymphoma

NK:

Natural killer

NOD-SCID:

Non-obese diabetic/severe combined immunodeficiency

PBL:

Peripheral blood lymphocytes

Relapsed/Refractory:

RR

TNF-α:

Tumor necrosis factor alpha

Treg:

Regulatory T cells

TAA:

Tumor associated antigens

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Funding

Some of the studies mentioned in this review were funded by Association for Research against Cancer (AIRC IG16891).The funders had no role in the preparation of this review.

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Authors and Affiliations

  1. Department of Haematology, King’s College Hospital NHS Foundation Trust and Sant′Andrea University Hospital, Rome, Italy

    Maria Christina Cox

  2. Dipartimento Di Oncologia e Medicina Molecolare, Istituto Superiore Di Sanità, Viale Regina Elena 299, 00161, Rome, Italy

    Caterina Lapenta & Stefano M. Santini

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  1. Maria Christina Cox
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  2. Caterina Lapenta
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  3. Stefano M. Santini
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MCC and SMS conceptualized the review. All authors contributed to the writing and editing of the review. All authors approved the final version.

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Correspondence to Caterina Lapenta or Stefano M. Santini.

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Stefano M. Santini received research funding from Celgene. All other authors declare that they have no conflict of interest.

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Cox, M.C., Lapenta, C. & Santini, S.M. Advances and perspectives of dendritic cell-based active immunotherapies in follicular lymphoma. Cancer Immunol Immunother 69, 913–925 (2020). https://doi.org/10.1007/s00262-020-02577-w

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