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Editorial
. 2023 Aug 30;11(10):369.
doi: 10.21037/atm-2023-5. Epub 2023 Mar 17.

Combination strategies incorporating oncolytic viruses and immune checkpoint inhibitors for advanced melanoma: what is the evidence?

Amarin Wongariyapak  1 , Victoria Roulstone  1 , Alan A Melcher  2 , Malin Pedersen  1   2 , Kevin J Harrington  1
Affiliations
Editorial

Combination strategies incorporating oncolytic viruses and immune checkpoint inhibitors for advanced melanoma: what is the evidence?

Amarin Wongariyapak et al. Ann Transl Med. .
No abstract available

Keywords: Advanced melanoma; immune checkpoint inhibition (ICI); oncolytic virus (OV); pembrolizumab; talimogene laherparepvec (T-VEC).

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Conflict of interest statement

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://atm.amegroups.com/article/view/10.21037/atm-2023-5/coif). VR acknowledges research funding and consulting fees from Replimune to institution. AAM, MP, and KJH reports grants from institution by Boerhringer-Ingelheim and Replimune. KJH reports consulting fees received from Arch Oncology, AstraZeneca, Boehringer-Ingelheim, Codiak Biosciences, F-start Therapeutics, Merck-Serono, MSD, Oncolys BioPharma, Pfizer, and Replimune, and payments or honoraria from Merck-Serono, MSD, and Replimune. AW has no conflicts of interest to declare.

Figures

Figure 1
Figure 1
Mechanisms of the combination between OVs and ICIs to activate anti-tumour immunity in advanced melanoma (8). (A) The tumour is in an immunologically cold state as it contains a low number of TILs and almost no PD-L1 expression. T-VEC is intratumorally administrated to the tumour site. The OVs infect tumour cells and viral replication occurs, resulting in lysis of tumour cells and, subsequently, the release of DAMPs, PAMPs, tumour antigens, and pro-inflammatory cytokines, including GM-CSF. T-VEC also upregulates membrane expression of PD-L1 and MHC class I molecules presenting tumour antigens. Furthermore, the progeny of T-VEC replication can infect adjacent tumour cells. (B) DAMP, PAMP and pro-inflammatory cytokines can recruit and stimulate APCs, particularly dendritic cells, to the tumour and enhance their migration to tumour-draining lymph nodes. The mature APCs can then present tumour antigen via MHC class II to CD4+ T cells and via MHC class I to CD8+ T cells, respectively. CD4+ T cells secrete IL-2 to support the expansion and activation of tumour-specific CD8+ T cells. Tumour-specific CD8+ T cells subsequently migrate to the tumour site. Therefore, an increase in TILs within the tumour site will alter the state of the tumour to become immunologically hot and primed for anti-PD-1/ICI efficacy. (C) Systemically administrated anti-PD-1 antibody will bind to the PD-1 molecules expressed on the membrane of CD8+ T cells within the tumour microenvironment. This antibody binding will interfere with the engagement of PD-L1 molecules on the tumour (and tumour microenvironmental) cells, and subsequently re-activate TILs and enhance their tumour killing efficacy. Created with BioRender.com. OV, oncolytic virus; ICI, immune checkpoint inhibitor; PD-1, programmed death-1; PD-L1, programmed death-ligand 1; T-VEC, Talimogene laherparepvec; TIL, tumour-infiltrating lymphocyte; MHC, major histocompatibility complex; DAMP, danger-associated molecular pattern; PAMP, pathogen-associated molecular pattern; GM-CSF, granulocyte-macrophage colony-stimulating factor; TLR, Toll-like receptor; PRR, pattern recognition receptor; APC, antigen-presenting cell.
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References

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