CCL8 enhances sensitivity of cutaneous squamous cell carcinoma to photodynamic therapy by recruiting M1 macrophages

Ji, Jie; Wang, Peiru; Zhou, Qian; Zhu, Lude; Zhang, Haiyan; Zhang, Yunfeng; Zheng, Zhe; Bhatta, Anil; Zhang, Goulong; Wang, Xiuli

doi:10.1016/j.pdpdt.2019.03.014

Cited by 20 publications

(10 citation statements)

References 27 publications

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“…For mφ-related DEGs, recent ndings emphasize that M1 mφs, M2 mφs and any intermediate states are not xed, frozen or immutable but remarkably plastic and transmutative (51), so the characteristics of certain mφ-associated genes have been found to be diverse, indeterminate or even paradoxical. For example, Ji et al reported that CCL8 could enhance the sensitivity of cutaneous squamous cell carcinoma to photodynamic therapy by recruiting M1 mφs, suggesting an antitumor role for CCL8 (52). In contrast, Zhang et al found that CCL8 secreted by TAMs could promote the invasion and stemness of glioblastoma via ERK1/2 signaling, which implied a protumor function for CCL8 (53).…”

Section: Discussionmentioning

confidence: 99%

A Novel Immune Checkpoint Siglec-15 Antibody Inhibits LUAD by Modulating mφ Polarization in TME

Xiao

Peng

Wang

et al. 2022

Preprint

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Background Siglec-15 (S15) is a type-I transmembrane protein and is considered a new candidate of immune checkpoint inhibitor for cancer immunotherapy. Methods In the present study, we first constructed and characterized a chimeric S15-specific monoclonal antibody (S15-4E6A). Then, the antitumor effectiveness and modulatory role of S15-4E6A in macrophages (mφs) were explored in vitro and in vivo. Finally, the underlying mechanism by which S15mAb inhibits LUAD was preliminarily explored. Results The results demonstrated the successful construction of S15-4E6A, and S15-4E6A exerted an efficacious tumor-inhibitory effect on LUAD cells and xenografts. S15-4E6A could promote M1-mφ polarization while inhibiting M2-mφ polarization, both in vitro and in vivo. Conclusions S15-based immunotherapy that functions by modulating mφ polarization may be a promising strategy for the treatment of S15-positive LUAD.

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Section: Discussionmentioning

confidence: 99%

A Novel Immune Checkpoint Siglec-15 Antibody Inhibits LUAD by Modulating mφ Polarization in TME

Xiao

Peng

Wang

et al. 2022

Preprint

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“…Our study found a positive correlation between CCL8 expression and levels of M1 macrophages, suggesting that CCL8 may help drive the anti-tumor efficacy of M1 macrophages in the TME. Indeed, one study found that CCL8 sensitized mice with cutaneous squamous cell carcinoma to photodynamic therapy by recruiting M1 macrophages [ 43 ]. In this way, our analyses suggest that CCL8 may influence immune activity in the TME, such as by promoting antitumor responses of M1 macrophages.…”

Section: Discussionmentioning

confidence: 99%

Correlation of CCL8 expression with immune cell infiltration of skin cutaneous melanoma: potential as a prognostic indicator and therapeutic pathway

Yang

Chen

et al. 2021

Cancer Cell Int

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Background The tumor microenvironment (TME) is critical in the progression and metastasis of skin cutaneous melanoma (SKCM). Differences in tumor-infiltrating immune cells (TICs) and their gene expression have been linked to cancer prognosis. Given that immunotherapy can be effective against SKCM, we aimed to identify key genes that regulate the immunological state of the TME in SKCM. Methods Data from 471 SKCM patients in the The Cancer Genome Atlas were analyzed using ESTIMATE algorithms to generate an ImmuneScore, StromalScore, and EstimateScore for each patient. Patients were classified into low- or high-score groups based on median values, then compared in order to identify differentially expressed genes (DEGs). Then a protein–protein interaction (PPI) network was developed, and a prognostic model was created using uni- and multivariate Cox regression as well as the least absolute shrinkage and selection operator (LASSO). Key DEGs were identified using the web-based tool GEPIA. Profiles of TIC subpopulations in each patient were analyzed using CIBORSORT, and possible correlations between key DEG expression and TICs were explored. Levels of CCL8 were determined in SKCM and normal skin tissue using immunohistochemistry. Results Two scores correlated positively with the prognosis of SKCM patients. Comparison of the low- and high-score groups revealed 1684 up-regulated and 18 down-regulated DEGs, all of which were enriched in immune-related functions. The prognostic model identified CCL8 as a key gene, which CIBERSORT found to correlate with M1 macrophages. Immunohistochemistry revealed strong expression in SKCM tissue, but failed to detect the protein in normal skin tissue. Conclusions CCL8 is a potential prognostic marker for SKCM, and it may become an effective target for melanoma in which M1 macrophages play an important role.

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“…In fact, recombinant CRT, upon peritumoral injection, has been shown to boost the therapeutic effect of PDT and/or PDT-generated cancer vaccines [83]. In addition, immunostimulants such as glycated chitosan [84], vitamin D3-binding protein-derived macrophage-activating factor (DBPMAF) [85], neutrophil promoting factor G-CSF [34,86], and Schizophillan (SPG) [87] have shown beneficial effects in the case of Photofrin-PDT, and CCL8 (monocyte chemoattractant protein-2) in the case of ALA-PDT [88].…”

Section: Immunostimulantsmentioning

confidence: 99%

Preclinical and Clinical Evidence of Immune Responses Triggered in Oncologic Photodynamic Therapy: Clinical Recommendations

Hernández

Ossendorp

et al. 2020

JCM

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Photodynamic therapy (PDT) is an anticancer strategy utilizing light-mediated activation of a photosensitizer (PS) which has accumulated in tumor and/or surrounding vasculature. Upon activation, the PS mediates tumor destruction through the generation of reactive oxygen species and tumor-associated vasculature damage, generally resulting in high tumor cure rates. In addition, a PDT-induced immune response against the tumor has been documented in several studies. However, some contradictory results have been reported as well. With the aim of improving the understanding and awareness of the immunological events triggered by PDT, this review focuses on the immunological effects post-PDT, described in preclinical and clinical studies. The reviewed preclinical evidence indicates that PDT is able to elicit a local inflammatory response in the treated site, which can develop into systemic antitumor immunity, providing long-term tumor growth control. Nevertheless, this aspect of PDT has barely been explored in clinical studies. It is clear that further understanding of these events can impact the design of more potent PDT treatments. Based on the available preclinical knowledge, recommendations are given to guide future clinical research to gain valuable information on the immune response induced by PDT. Such insights directly obtained from cancer patients can only improve the success of PDT treatment, either alone or in combination with immunomodulatory approaches.

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CCL8 enhances sensitivity of cutaneous squamous cell carcinoma to photodynamic therapy by recruiting M1 macrophages

Cited by 20 publications

References 27 publications

A Novel Immune Checkpoint Siglec-15 Antibody Inhibits LUAD by Modulating mφ Polarization in TME

A Novel Immune Checkpoint Siglec-15 Antibody Inhibits LUAD by Modulating mφ Polarization in TME

Correlation of CCL8 expression with immune cell infiltration of skin cutaneous melanoma: potential as a prognostic indicator and therapeutic pathway

Preclinical and Clinical Evidence of Immune Responses Triggered in Oncologic Photodynamic Therapy: Clinical Recommendations

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