Inhibition of lymphangiogenesis impairs antitumour effects of photodynamic therapy and checkpoint inhibitors in mice

Muchowicz, Angelika; Wachowska, Malgorzata; Stachura, Joanna; Tonecka, Katarzyna; Gabrysiak, Magdalena; Wołosz, Dominika; Pilch, Zofia; Kilarski, Witold W.; Boon, Louis; Klaus, Tomasz; Gołąb, Jakub

doi:10.1016/j.ejca.2017.06.004

Cited by 45 publications

(35 citation statements)

References 27 publications

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“…This ultimately led to exacerbation of renal inflammation and fibrosis, rather than inflammation resolution [8]. A lot of recent literature also supports our view [54,55].…”

Section: Lymphangiogenesis and Kidney Diseasesupporting

confidence: 81%

“…Inducing lymphangiogenesis has been shown to decrease intersti-tial fluid accumulation and attenuate inflammation [56]. Muchowicz et al [54] reported that sustained inhibition of lymphangiogenesis by soluble VEGFR-3 also inhibited the capacity of DCs translocating into local lymph nodes and resulted in less tumor antigen-specific CD8+ T-cell response. Lymphangiogenesis is also associated with chronic kidney allograft injury, and sirolimus has been identified as a potent inhibitor of lymphangiogenesis in renal allografts by blocking the VEGF-C/VEGFR-3 pathway [57].…”

Section: Prospect For the Futurementioning

confidence: 99%

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Lymphatic Vessels Enhancing Adaptive Immunity Deteriorates Renal Inflammation and Renal Fibrosis

Pei

Zeng

et al. 2020

Kidney Dis

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Background: Lymphatic vessels transport lymph away from microvascular beds into the cardiovascular system. The basic function of the lymphatic system include absorption of wa ter and macromolecules in the interstitial fluid, which plays an important role in maintaining osmotic balance of the body. Recent studies have shown that lymphangiogenesis is associated with tumor metabolism, injury repair, and chron ic inflammation, and deteriorates disease progression via immune cell trafficking. Summary: Renal interstitial lymph angiogenesis is found in patients with chronic kidney dis ease and a series of animal models of renal fibrosis. Lymphat ic vessels transfer antigen and antigenpresenting cells from peripheral tissues to lymph nodes, which initiates adaptive immunity and in turn deteriorates renal inflammation and renal fibrosis, even in nonautoimmune renal diseases. Key Messages: This review summarizes the latest findings on how lymphatics participate in the progression of chronic kid ney disease. This discussion will serve to highlight the role of adaptive immunity in noninfectious and nonautoimmune nephropathy, in order to provide new ideas and methods for prevention and treatment of kidney diseases.

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“…This ultimately led to exacerbation of renal inflammation and fibrosis, rather than inflammation resolution [8]. A lot of recent literature also supports our view [54,55].…”

Section: Lymphangiogenesis and Kidney Diseasesupporting

confidence: 81%

Section: Prospect For the Futurementioning

confidence: 99%

Lymphatic Vessels Enhancing Adaptive Immunity Deteriorates Renal Inflammation and Renal Fibrosis

Pei

Zeng

et al. 2020

Kidney Dis

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“…In a recent study by Bao et al , tumor vasculature‐targeted PDT was combined with immune checkpoint blockade (discussed in a later section) which resulted in the effective control of primary 4T1 tumors, as well as disseminated 4T1 tumor metastases. Interestingly, in another study by Muchowicz et al using verteporfin‐based PDT of orthotopic mammary tumors, the sustained inhibition of lymphangiogenesis in fact significantly impaired the outcome of PDT. The study also found a decreased number of tumor‐infiltrating immune cells, suggesting a role for intact lymphatic vessels in eliciting an antitumor immune response.…”

Section: Fundamentals Of Photobiology and Photochemistrymentioning

confidence: 99%

The Course of Immune Stimulation by Photodynamic Therapy: Bridging Fundamentals of Photochemically Induced Immunogenic Cell Death to the Enrichment of T‐Cell Repertoire

Nath

Obaid

Hasan

2019

Photochem & Photobiology

102

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Photodynamic therapy (PDT) is a potentially immunogenic and FDA‐approved antitumor treatment modality that utilizes the spatiotemporal combination of a photosensitizer, light and oftentimes oxygen, to generate therapeutic cytotoxic molecules. Certain photosensitizers under specific conditions, including ones in clinical practice, have been shown to elicit an immune response following photoillumination. When localized within tumor tissue, photogenerated cytotoxic molecules can lead to immunogenic cell death (ICD) of tumor cells, which release damage‐associated molecular patterns and tumor‐specific antigens. Subsequently, the T‐lymphocyte (T cell)–mediated adaptive immune system can become activated. Activated T cells then disseminate into systemic circulation and can eliminate primary and metastatic tumors. In this review, we will detail the multistage cascade of events following PDT of solid tumors that ultimately lead to the activation of an antitumor immune response. More specifically, we connect the fundamentals of photochemically induced ICD with a proposition on potential mechanisms for PDT enhancement of the adaptive antitumor response. We postulate a hypothesis that during the course of the immune stimulation process, PDT also enriches the T‐cell repertoire with tumor‐reactive activated T cells, diversifying their tumor‐specific targets and eliciting a more expansive and rigorous antitumor response. The implications of such a process are likely to impact the outcomes of rational combinations with immune checkpoint blockade, warranting investigations into T‐cell diversity as a previously understudied and potentially transformative paradigm in antitumor photodynamic immunotherapy.

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“…Furthermore, melanomas implanted in K14‐VEGFR3‐Ig mice exhibited drastically decreased immune cytotoxicity . Along this line, the inhibition of LV regeneration by photodynamic therapy impaired the development of antitumor immunity …”

Section: Functional Heterogeneity Of Tumor Lymphangiogenesismentioning

confidence: 98%

“…Furthermore, melanomas implanted in K14-VEGFR3-Ig mice exhibited drastically decreased immune cytotoxicity 40. Along this line, the inhibition of LV regeneration by photodynamic therapy impaired the development of antitumor immunity 72. Thus, LV may have paradoxical roles in tumor progression, not only allowing metastatic escape but also enhancing the immune recognition and critical checkpoints in antitumor responses.…”

mentioning

confidence: 99%

Heterogeneity of tumor lymphangiogenesis: Progress and prospects

Luo

2018

Cancer Science

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Lymphangiogenesis and increased expression of lymphangiogenic growth factors are associated with high rates of lymph node (LN) metastasis and with poor prognosis in some, but not all, solid tumors. In addition to its involvement in metastasis, lymphangiogenesis has been shown to have other roles in tumor pathogenesis, such as the niche function of tumor stem cells and regulatory functions of antitumor immune responses. In contrast, evidence has accumulated that tumor‐induced lymphangiogenesis displays the heterogeneity in gene signature, structure, cellular origins and functional plasticity. This review summarizes the advances in the research on the heterogeneity of tumor lymphangiogenesis and discusses how it may contribute to functional complexity and multiplicity of lymphangiogenesis in tumor progression.

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Inhibition of lymphangiogenesis impairs antitumour effects of photodynamic therapy and checkpoint inhibitors in mice

Cited by 45 publications

References 27 publications

Lymphatic Vessels Enhancing Adaptive Immunity Deteriorates Renal Inflammation and Renal Fibrosis

Lymphatic Vessels Enhancing Adaptive Immunity Deteriorates Renal Inflammation and Renal Fibrosis

The Course of Immune Stimulation by Photodynamic Therapy: Bridging Fundamentals of Photochemically Induced Immunogenic Cell Death to the Enrichment of T‐Cell Repertoire

Heterogeneity of tumor lymphangiogenesis: Progress and prospects

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