Stimulation of dendritic cells by DAMPs in ALA-PDT treated SCC tumor cells

Wang, Xiaojie; Ji, Jie; Zhang, Haiyan; Fan, Zhixia; Zhang, Linglin; Shi, Lei; Zhou, Feifan; Chen, Wei R.; Wang, Hongwei; Wang, Xiuli

doi:10.18632/oncotarget.5975

Cited by 66 publications

(53 citation statements)

References 47 publications

(59 reference statements)

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“…HMGB1 has been shown to be important for activation of myeloid and plasmacytoid DCs [25, 31, 42–46]. In our model, DC maturation with up-regulation of CD40, CD80 and CD86 was measured in tumor draining LN after IL PV-10.…”

Section: Discussionmentioning

confidence: 98%

Intralesional rose bengal in melanoma elicits tumor immunityviaactivation of dendritic cells by the release of high mobility group box 1

et al. 2016

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Intralesional (IL) therapy is under investigation to treat dermal and subcutaneous metastatic cancer. Rose bengal (RB) is a staining agent that was originally used by ophthalmologists and in liver function studies. IL injection of RB has been shown to induce regression of injected and uninjected tumors in murine models and clinical trials. In this study, we have shown a mechanism of tumor-specific immune response induced by IL RB. In melanoma-bearing mice, IL RB induced regression of injected tumor and inhibited the growth of bystander lesions mediated by CD8+ T cells. IL RB resulted in necrosis of tumor cells and the release of High Mobility Group Box 1 (HMGB1), with increased dendritic cell (DC) infiltration into draining lymph nodes and the activation of tumor-specific T cells. Treatment of DC with tumor supernatants increased the ability of DCs to stimulate T cell proliferation, and blockade of HMGB1 in the supernatants suppressed DC activity. Additionally, increased HMGB1 levels were measured in the sera of melanoma patients treated with IL RB. These results support the role of IL RB to activate dendritic cells at the site of tumor necrosis for the induction of a systemic anti-tumor immune response.

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Section: Discussionmentioning

confidence: 98%

Intralesional rose bengal in melanoma elicits tumor immunityviaactivation of dendritic cells by the release of high mobility group box 1

et al. 2016

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“…This exposure of immunogenic molecules after NB-PDT was the next event explored in this study. Conventional PDT is described to induce exposure of HSP70, among other chaperones, on the membrane of tumor cells [28][29][30][31]. Membrane exposure of HSP70 was indeed observed on A431 and scc-U8 cells treated with mild NB-PDT, although it was more evident on the high EGFR-expressing cells at the early timepoint studied (Figure 2a,b).…”

Section: Discussionmentioning

confidence: 99%

The Potential of Nanobody-Targeted Photodynamic Therapy to Trigger Immune Responses

Hernández

Angelier

D’Ondes

et al. 2020

Cancers

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M.L.A.); a.dimaggio@students.uu.nl (A.D.M.); Y.Yu@uu.nl (Y.Y.)Abstract: Nanobody-targeted photodynamic therapy (NB-PDT) has been recently developed as a more tumor-selective approach rather than conventional photodynamic therapy (PDT). NB-PDT uses nanobodies that bind to tumor cells with high affinity, to selectively deliver a photosensitizer, i.e., a chemical which becomes cytotoxic when excited with light of a particular wavelength. Conventional PDT has been reported to be able to induce immunogenic cell death, characterized by the exposure/release of damage-associated molecular patterns (DAMPs) from dying cells, which can lead to antitumor immunity. We explored this aspect in the context of NB-PDT, targeting the epidermal growth factor receptor (EGFR), using high and moderate EGFR-expressing cells. Here we report that, after NB-PDT, the cytoplasmic DAMP HSP70 was detected on the cell membrane of tumor cells and the nuclear DAMP HMGB1 was found in the cell cytoplasm. Furthermore, it was shown that NB-PDT induced the release of the DAMPs HSP70 and ATP, as well as the pro-inflammatory cytokines IL-1β and IL-6. Conditioned medium from high EGFR-expressing tumor cells treated with NB-PDT led to the maturation of human dendritic cells, as indicated by the upregulation of CD86 and MHC II on their cell surface, and the increased release of IL-12p40 and IL-1β. Subsequently, these dendritic cells induced CD4+ T cell proliferation, accompanied by IFNγ release. Altogether, the initial steps reported here point towards the potential of NB-PDT to stimulate the immune system, thus giving this selective-local therapy a systemic reach.Despite being a selective and controllable treatment against tumor cells, therapies known to be considerably aggressive towards all tissues (i.e., chemo-and radiotherapy) are still the mainstream clinical practice, when it comes to combat cancer [5]. Some current barriers for the establishment of PDT in routine practice are the required technology, complex dosimetry, limited tissue penetration of light and/or PS, lack of tumor specificity and prolonged skin photosensitivity [1,5]. Efforts have been put into improving the selectivity of PDT towards the cancer cells by using antibodies, an approach which is now in phase II clinical trial (NCT02422979) [6]. Conjugation of a water-soluble PS (IRDye700DX) to an antibody allows the PS to be specifically delivered to cancer cells overexpressing a certain antigen on the cell membrane. In this manner, two levels of specificity are established: the delivery of PS to target-expressing cells and the local application of light at the tumor site.Another strategy to render PDT more tumor-selective is nanobody-targeted PDT (NB-PDT), which also utilizes the near-infrared PS IRDye700DX. In this case, however, a nanobody is used to provide the first level of specificity [7,8]. NBs are the smallest binding domains found in nature (~15 kDa) and consist uniquely of the variable domain of heavy chain antibodies present in Camelids [9]. The use of a NB for PDT brings a ...

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“…CD40, CD80, and CD86 expression are essential for T lymphocyte stimulation [42]. In addition to being a maturation marker, CD83 modulates the immune response by stimulating both naive and memory T cells [43]. CD83 expression was also enhanced by the drug combination.…”

Section: Discussionmentioning

confidence: 99%

Blocking drug-induced autophagy with chloroquine in HCT-116 colon cancer cells enhances DC maturation and T cell responses induced by tumor cell lysate

Ramirez

Romagnoli

Falasco

et al. 2020

International Immunopharmacology

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Autophagy is an important mechanism for tumor escape, allowing tumor cells to recover from the damage induced by chemotherapy, radiation therapy, and immunotherapy and contributing to the development of resistance. The pharmacological inhibition of autophagy contributes to increase the efficacy of antineoplastic agents. Exposing tumor cells to low concentrations of select autophagy-inducing antineoplastic agents increases their immunogenicity and enhances their ability to stimulate dendritic cell (DC) maturation. We tested whether the application of an autophagy-inhibiting agent, chloroquine (CQ), in combination with low concentrations of 5-fluorouracil (5-FU) increases the ability of tumor cells to induce DC maturation. DCs sensitized with the lysate of HCT-116 cells previously exposed to such a combination enhanced the DC maturation/activation ability. These matured DCs also increased the allogeneic responsiveness of both CD4+ and CD8+ T cells, which showed a greater proliferative response than those from DCs sensitized with control lysates. The T cells expanded in such cocultures were CD69+ and PD-1-and produced higher levels of IFN-γ and lower levels of IL-10, consistent with the preferential activation of Th1 cells. Cocultures of autologous DCs and lymphocytes improved the generation of cytotoxic T lymphocytes, as assessed by the expression of CD107a, perforin, and granzyme B. The drug combination increased the expression of genes related to the CEACAM family (BECN1, ATGs, MAPLC3B, ULK1, SQSTM1) and tumor suppressors (PCBP1). Furthermore, the decreased expression of genes related to metastasis and tumor progression (BNIP3, BNIP3L, FOSL2, HES1, LAMB3, LOXL2, NDRG1, P4HA1, PIK3R2) was noted. The combination of 5-FU and CQ increases the ability of tumor cells to drive DC maturation and enhances the ability of DCs to stimulate T cell responses.

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Stimulation of dendritic cells by DAMPs in ALA-PDT treated SCC tumor cells

Cited by 66 publications

References 47 publications

Intralesional rose bengal in melanoma elicits tumor immunityviaactivation of dendritic cells by the release of high mobility group box 1

Intralesional rose bengal in melanoma elicits tumor immunityviaactivation of dendritic cells by the release of high mobility group box 1

The Potential of Nanobody-Targeted Photodynamic Therapy to Trigger Immune Responses

Blocking drug-induced autophagy with chloroquine in HCT-116 colon cancer cells enhances DC maturation and T cell responses induced by tumor cell lysate

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