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Review
. 2023 Aug 24:14:1249330.
doi: 10.3389/fimmu.2023.1249330. eCollection 2023.

Combining PD-1/PD-L1 blockade with type I interferon in cancer therapy

Affiliations
Review

Combining PD-1/PD-L1 blockade with type I interferon in cancer therapy

Ali Razaghi et al. Front Immunol. .

Abstract

PD-1 and PD-L1 are crucial regulators of immunity expressed on the surface of T cells and tumour cells, respectively. Cancer cells frequently use PD-1/PD-L1 to evade immune detection; hence, blocking them exposes tumours to be attacked by activated T cells. The synergy of PD-1/PD-L1 blockade with type I interferon (IFN) can improve cancer treatment efficacy. Type I IFN activates immune cells boosts antigen presentation and controls proliferation. In addition, type I IFN increases tumour cell sensitivity to the blockade. Combining the two therapies increases tumoral T cell infiltration and activation within tumours, and stimulate the generation of memory T cells, leading to prolonged patient survival. However, limitations include heterogeneous responses, the need for biomarkers to predict and monitor outcomes, and adverse effects and toxicity. Although treatment resistance remains an obstacle, the combined therapeutic efficacy of IFNα/β and PD-1/PD-L1 blockade demonstrated considerable benefits across a spectrum of cancer types, notably in melanoma. Overall, the phases I and II clinical trials have demonstrated safety and efficiency. In future, further investigations in clinical trials phases III and IV are essential to compare this combinatorial treatment with standard treatment and assess long-term side effects in patients.

Keywords: PD-1; PD-L1; cancer; immunotherapy; interferon; interferon a (IFNa).

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Conflict of interest statement

The authors have no conflict of interest. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Schematic overview of cellular interaction after combinational treatment with type I IFN and PD-1/PD-L1 blockade. The treatment with anti-PD-1/PD-L1 Abs saves CD8+ T cells from exhaustion while targeting IFNα to the tumour microenvironment promotes the release of IP-10 from antigen-positive tumour cells increases T cell infiltration and improves CD4+ T cell function for anti-tumour immunity. Furthermore, MHC class I are upregulated on cancer cells increasing antitumor CD8+ T cell response. Also, IFNα activates DC-induced cross-priming by releasing IL-6.

References

    1. Yi M, Zheng X, Niu M, Zhu S, Ge H, Wu K. Combination strategies with PD-1/PD-L1 blockade: current advances and future directions. Mol Cancer (2022) 21:28. doi: 10.1186/s12943-021-01489-2 - DOI - PMC - PubMed
    1. Tumeh PC, Harview CL, Yearley JH, Shintaku IP, Taylor EJ, Robert L, et al. PD-1 blockade induces responses by inhibiting adaptive immune resistance. Nature (2014) 515:568–71. doi: 10.1038/nature13954 - DOI - PMC - PubMed
    1. Lei Q, Wang D, Sun K, Wang L, Zhang Y. Resistance mechanisms of anti-PD1/PDL1 therapy in solid tumors. Front Cell Dev Biol (2020) 8:672. doi: 10.3389/fcell.2020.00672 - DOI - PMC - PubMed
    1. Huang AC, Postow MA, Orlowski RJ, Mick R, Bengsch B, Manne S, et al. T-cell invigoration to tumour burden ratio associated with anti-PD-1 response. Nature (2017) 545:60–5. doi: 10.1038/nature22079 - DOI - PMC - PubMed
    1. Schiavoni G, Mattei F, Gabriele L. Type I interferons as stimulators of DC-mediated cross-priming: impact on anti-tumor response. Front Immunol (2013) 4:483. doi: 10.3389/fimmu.2013.00483 - DOI - PMC - PubMed

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