Photodynamic Therapy and Immune Checkpoint Blockade<sup>†</sup>

Cramer, Gwendolyn M.; Moon, Edmund K.; Cengel, Keith A.; Busch, Theresa M.

doi:10.1111/php.13300

Cited by 64 publications

(37 citation statements)

References 59 publications

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“…Antitumor physical therapy can cause the death of tumor cells and the release of tumor antigens, which up-regulates the expression of MHC-I complex on tumor cells and promotes the maturation of antigen-presenting cells. Subsequently, the activation and proliferation of effector T cells are initiated by antigen-presenting cells, thus exerting anti-tumor immune response ( Brodin, Guha & Tomé, 2015 ; Chen et al, 2020 ; Cramer et al, 2020 ; Eckert et al, 2019 ). However, studies have shown that radiotherapy and PDT can up-regulate the expression of PDL1 in tumor, weakening the anti-tumor immune response ( Deng et al, 2014 ; O’Shaughnessy et al, 2018 ).…”

Section: Survey Methodologymentioning

confidence: 99%

The regulation of immune checkpoints by the hypoxic tumor microenvironment

et al. 2021

PeerJ

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The tumor microenvironment (TME) influences the occurrence and progression of tumors, and hypoxia is an important characteristic of the TME. The expression of programmed death 1 (PD1)/programmed death-ligand 1 (PDL1), cytotoxic T-lymphocyte-associated antigen 4 (CTLA4), and other immune checkpoints in hypoxic malignant tumors is often significantly increased, and is associated with poor prognosis. The application of immune checkpoint inhibitors (ICIs) for treating lung cancer, urothelial carcinoma, and gynecological tumors has achieved encouraging efficacy; however, the rate of efficacy of ICI single-drug treatment is only about 20%. In the present review, we discuss the possible mechanisms by which the hypoxic TME regulates immune checkpoints. By activating hypoxia-inducible factor-1α (HIF-1α), regulating the adenosine (Ado)-A2aR pathway, regulating the glycolytic pathway, and driving epithelial-mesenchymal transition (EMT) and other biological pathways, hypoxia regulates the expression levels of CTLA4, PD1, PDL1, CD47, lymphocyte activation gene 3 (LAG3), T-cell immunoglobulin and mucin domain 3 (TIM3), and other immune checkpoints, which interfere with the immune effector cell anti-tumor response and provide convenient conditions for tumors to escape immune surveillance. The combination of HIF-1α inhibitors, Ado-inhibiting tumor immune microenvironment regulatory drugs, and other drugs with ICIs has good efficacy in both preclinical studies and phase I-II clinical studies. Exploring the effects of TME hypoxia on the expression of immune checkpoints and the function of infiltrating immune cells has greatly clarified the relationship between the hypoxic TME and immune escape, which is of great significance for the development of new drugs and the search for predictive markers of the efficacy of immunotherapy for treating malignant tumors. In the future, combination therapy with hypoxia pathway inhibitors and ICIs may be an effective anti-tumor treatment strategy.

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Section: Survey Methodologymentioning

confidence: 99%

The regulation of immune checkpoints by the hypoxic tumor microenvironment

et al. 2021

PeerJ

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“…Various studies have profoundly demonstrated that PDT can cause immunogenic cell death (ICD) to release damage-associated molecules and consequently improve the immunogenicity of tumors 169 . Moreover, the combination of PDT with checkpoint-blockade immunotherapy can better eliminate primary tumors, inhibit metastasis, and prevent recurrence 179 . For example, Xu et al 180 synthesized UCNPs to simultaneously load Ce6 and imiquimod (R837, a Toll-like-receptor-7 agonist) for immuno-PDT.…”

Section: Pdt-involved Multimodal Therapiesmentioning

confidence: 99%

Recent advances in innovative strategies for enhanced cancer photodynamic therapy

et al. 2021

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Photodynamic therapy (PDT), a non-invasive therapeutic modality, has received increasing attention owing to its high selectivity and limited side effects. Although significant clinical research progress has been made in PDT, the breadth and depth of its clinical application have not been fully realized due to the limitations such as inadequate light penetration depth, non-targeting photosensitizers (PSs), and tumor hypoxia. Consequently, numerous investigations put their emphasis on innovative strategies to overcome the aforementioned limitations and enhance the therapeutic effect of PDT. Herein, up-to-date advances in these innovative methods for PDT are summarized by introducing the design of PS systems, their working mechanisms and application examples. In addition, current challenges of these innovative strategies for clinical application, and future perspectives on further improvement of PDT are also discussed.

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“…These factors could serve to promote synergy between PDT and immune checkpoint blockade. 76 Currently, the main ICB therapy using indoleamine 2,3-dioxygenase (IDO), anti-programmed death-ligand 1 (αPD-L1), anti-programmed death 1 (αPD-1), and anticytotoxic T lymphocyte-associated antigen 4 (αCTLA-4) antibodies have exhibited great capability in clinics. Treated antibodies can block IDO, 77 CTLA-4, 78 or PD-1, 79 and dramatically lengthen the overall survival of various cancer patients.…”

Section: Strategies Of Relieving Immunoregulatory Suppressionmentioning

confidence: 99%

Nanomaterials-Based Photodynamic Therapy with Combined Treatment Improves Antitumor Efficacy Through Boosting Immunogenic Cell Death

Fan¹,

Liu²,

Xu³

et al. 2021

IJN

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Benefiting from the rapid development of nanotechnology, photodynamic therapy (PDT) is arising as a novel non-invasive clinical treatment for specific cancers, which exerts direct efficacy in destroying primary tumors by generating excessive cytotoxic reactive oxygen species (ROS). Notably, PDT-induced cell death is related to T cell-mediated antitumor immune responses through induction of immunogenic cell death (ICD). However, ICD elicited via PDT is not strong enough and is limited by immunosuppressive tumor microenvironment (ITM). Therefore, it is necessary to improve PDT efficacy through enhancing ICD with the combination of synergistic tumor therapies. Herein, the recent progress of nanomaterials-based PDT combined with chemotherapy, photothermal therapy, radiotherapy, and immunotherapy, employing ICD-boosted treatments is reviewed. An outlook about the future application in clinics of nanomaterials-based PDT strategies is also mentioned.

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Photodynamic Therapy and Immune Checkpoint Blockade^†

Cited by 64 publications

References 59 publications

The regulation of immune checkpoints by the hypoxic tumor microenvironment

The regulation of immune checkpoints by the hypoxic tumor microenvironment

Recent advances in innovative strategies for enhanced cancer photodynamic therapy

Nanomaterials-Based Photodynamic Therapy with Combined Treatment Improves Antitumor Efficacy Through Boosting Immunogenic Cell Death

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Photodynamic Therapy and Immune Checkpoint Blockade†

Cited by 64 publications

References 59 publications

The regulation of immune checkpoints by the hypoxic tumor microenvironment

The regulation of immune checkpoints by the hypoxic tumor microenvironment

Recent advances in innovative strategies for enhanced cancer photodynamic therapy

Nanomaterials-Based Photodynamic Therapy with Combined Treatment Improves Antitumor Efficacy Through Boosting Immunogenic Cell Death

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Resources

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Photodynamic Therapy and Immune Checkpoint Blockade^†