Dual photothermal MDSCs-targeted immunotherapy inhibits lung immunosuppressive metastasis by enhancing T-cell recruitment

Domvri, Kalliopi; Petanidis, Savvas; Anestakis, Doxakis; Porpodis, Κonstantinos; Bai, Chong; Zarogoulidis, Paul; Freitag, Lutz; Hohenforst-Schmidt, Wolfgang; Katopodi, Theodora

doi:10.1039/d0nr00080a

Cited by 30 publications

(23 citation statements)

References 38 publications

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“…34 CD8 + TEMs have the ability to persist for years and kill tumour and infected cells, to protect against LC and be the predictive factor of early response to postradiotherapy lung metastasis. [35][36][37] The downregulation of naïve CD8 + T cells and CTL happens in chronic lung diseases including LC and COPD, of which naïve CD8 + T cells can induce systemic antitumour immunity and inhibit tumour growth. 38 The number of CD4 + TCM and CD4 + TEM varied among lung diseases, of which quiescent CD4 + TEMs are present within the microenvironment of human LC and contribute to tumour cell apoptosis by releasing inflammatory mediators, secreting IFN-γ and induce cell proliferation.…”

Section: Discussionmentioning

confidence: 99%

A cellular census of human peripheral immune cells identifies novel cell states in lung diseases

Song

Yan

et al. 2021

Clinical & Translational Med

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Increasing evidence supports a central role of the immune system in lung diseases. Understanding how immunological alterations between lung diseases provide opportunities for immunotherapy. Exhausted T cells play a key role of immune suppression in lung cancer and chronic obstructive pulmonary disease was proved in our previous study. The present study aims to furthermore define molecular landscapes and heterogeneity of systemic immune cell target proteomic and transcriptomic profiles and interactions between circulating immune cells and lung residential cells in various lung diseases. We firstly measured target proteomic profiles of circulating immune cells from healthy volunteers and patients with stable pneumonia, stable asthma, acute asthma, acute exacerbation of chronic obstructive pulmonary disease, chronic obstructive pulmonary disease and lung cancer, using single‐cell analysis by cytometry by time‐of‐flight with 42 antibodies. The nine immune cells landscape was mapped among those respiratory system diseases, including CD4 + T cells, CD8 + T cells, dendritic cells, B cells, eosinophil, γδT cells, monocytes, neutrophil and natural killer cells. The double‐negative T cells and exhausted CD4 + central memory T cells subset were identified in patients with acute pneumonia. This T subset expressed higher levels of T‐cell immunoglobulin and mucin domain‐containing protein 3 (Tim3) and T‐cell immunoreceptor with Ig and ITIM domains (TIGIT) in patients with acute pneumonia and stable pneumonia. Biological processes and pathways of immune cells including immune response activation, regulation of cell cycle and pathways in cancer in peripheral blood immune cells were defined by bulk RNA sequencing (RNA‐seq). The heterogeneity among immune cells including CD4 + , CD8 + T cells and NK T cells by single immune cell RNA‐seq with significant difference was found by single‐cell sequencing. The effect of interstitial telocytes on the immune cell types and immune function was finally studied and the expressions of CD8a and chemokine C–C motif receptor 7 (CCR7) were increased significantly in co‐cultured groups. Our data indicate that proteomic and transcriptomic profiles and heterogeneity of circulating immune cells provides new insights for understanding new molecular mechanisms of immune cell function, interaction and modulation as a source to identify and develop biomarkers and targets for lung diseases.

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Section: Discussionmentioning

confidence: 99%

A cellular census of human peripheral immune cells identifies novel cell states in lung diseases

Song

Yan

et al. 2021

Clinical & Translational Med

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“…94 Greater maturation of dendritic cells triggered by Yining Zhu designed Al-BSA-Ce6NPs translates into higher levels of tumor and lymph node infiltration through CD8 + and CD4 + T cells which aims to compete for melanoma by albumin-biomineralized nanoparticles to synergize PTT and immunotherapy. 95…”

Section: Dovepressmentioning

confidence: 99%

<p>Pathological Mechanism of Photodynamic Therapy and Photothermal Therapy Based on Nanoparticles</p>

Hou

Yang

Liu

et al. 2020

IJN

218

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The ultimate goal of phototherapy based on nanoparticles, such as photothermal therapy (PTT) which generates heat and photodynamic therapy (PDT) which not only generates reactive oxygen species (ROS) but also induces a variety of anti-tumor immunity, is to kill tumors. In addition, due to strong efficacy in clinical treatment with minimal invasion and negligible side effects, it has received extensive attention and research in recent years. In this paper, the generations of nanomaterials in PTT and PDT are described separately. In clinical application, according to the different combination pathway of nanoparticles, it can be used to treat different diseases such as tumors, melanoma, rheumatoid and so on. In this paper, the mechanism of pathological treatment is described in detail in terms of inducing apoptosis of cancer cells by ROS produced by PDT, immunogenic cell death to provoke the maturation of dendritic cells, which in turn activate production of CD4+ T cells, CD8+T cells and memory T cells, as well as inhibiting heat shock protein (HSPs), STAT3 signal pathway and so on.

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“…Nowadays, nanocarriers employing different options to target MDSCs, promote MD-SCs maturation and modulate their function to regress tumor progression and angiogenesis [120]. Furthermore, MDSCs cell membrane coated iron oxide magnetic nanoparticles successfully evaded the immune system, actively targeted cancer cells along with magnetic and photothermal-induced ablation of the cancer cells [121].…”

Section: Myeloid-derived Suppressor Cells (Mdscs)mentioning

confidence: 99%

Onco-Receptors Targeting in Lung Cancer via Application of Surface-Modified and Hybrid Nanoparticles: A Cross-Disciplinary Review

et al. 2021

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Lung cancer is among the most prevalent and leading causes of death worldwide. The major reason for high mortality is the late diagnosis of the disease, and in most cases, lung cancer is diagnosed at fourth stage in which the cancer has metastasized to almost all vital organs. The other reason for higher mortality is the uptake of the chemotherapeutic agents by the healthy cells, which in turn increases the chances of cytotoxicity to the healthy body cells. The complex pathophysiology of lung cancer provides various pathways to target the cancerous cells. In this regard, upregulated onco-receptors on the cell surface of tumor including epidermal growth factor receptor (EGFR), integrins, transferrin receptor (TFR), folate receptor (FR), cluster of differentiation 44 (CD44) receptor, etc. could be exploited for the inhibition of pathways and tumor-specific drug targeting. Further, cancer borne immunological targets like T-lymphocytes, myeloid-derived suppressor cells (MDSCs), tumor-associated macrophages (TAMs), and dendritic cells could serve as a target site to modulate tumor activity through targeting various surface-expressed receptors or interfering with immune cell-specific pathways. Hence, novel approaches are required for both the diagnosis and treatment of lung cancers. In this context, several researchers have employed various targeted delivery approaches to overcome the problems allied with the conventional diagnosis of and therapy methods used against lung cancer. Nanoparticles are cell nonspecific in biological systems, and may cause unwanted deleterious effects in the body. Therefore, nanodrug delivery systems (NDDSs) need further advancement to overcome the problem of toxicity in the treatment of lung cancer. Moreover, the route of nanomedicines’ delivery to lungs plays a vital role in localizing the drug concentration to target the lung cancer. Surface-modified nanoparticles and hybrid nanoparticles have a wide range of applications in the field of theranostics. This cross-disciplinary review summarizes the current knowledge of the pathways implicated in the different classes of lung cancer with an emphasis on the clinical implications of the increasing number of actionable molecular targets. Furthermore, it focuses specifically on the significance and emerging role of surface functionalized and hybrid nanomaterials as drug delivery systems through citing recent examples targeted at lung cancer treatment.

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Dual photothermal MDSCs-targeted immunotherapy inhibits lung immunosuppressive metastasis by enhancing T-cell recruitment

Abstract: Biodegradable MDSCs-targeted nanospheres containing l-Norvaline and Sunitinib in order to facilitate inhibition of tumor-supporting immunosuppression.

Cited by 30 publications

References 38 publications

A cellular census of human peripheral immune cells identifies novel cell states in lung diseases

A cellular census of human peripheral immune cells identifies novel cell states in lung diseases

<p>Pathological Mechanism of Photodynamic Therapy and Photothermal Therapy Based on Nanoparticles</p>

Onco-Receptors Targeting in Lung Cancer via Application of Surface-Modified and Hybrid Nanoparticles: A Cross-Disciplinary Review

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