αvβ3-integrin regulates PD-L1 expression and is involved in cancer immune evasion

Vannini, Andrea; Leoni, Valerio; Barboni, Catia; Sanapo, Mara; Zaghini, Anna; Malatesta, Paolo; Campadelli-Fiume, Gabriella; Gianni, Tatiana

doi:10.1073/pnas.1901931116

Cited by 57 publications

(48 citation statements)

References 55 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As a possible explanation, one of the known integrin targets for this class of peptides, integrin α v β 3 , 34 has been reported to function as a co-receptor in IFNγ-mediated stimulation of PD-L1 expression and, thus, some signaling by IFNγ may be directly inhibited by AXT201. 72 Nonetheless, the extent to which AXT201 inhibits pro-immune functions of IFNγ remains to be determined.…”

Section: Discussionmentioning

confidence: 99%

Regulation of the tumor immune microenvironment and vascular normalization in TNBC murine models by a novel peptide

et al. 2020

View full text Add to dashboard Cite

Triple-negative breast cancer (TNBC) is a highly metastatic and aggressive disease with limited treatment options. Recently, the combination of the immune checkpoint inhibitor (ICI) atezolizumab (anti-PD-L1) with nab-paclitaxel was approved following a clinical trial that showed response rates in at least 43% of patients. While this approval marks a major advance in the treatment of TNBC it may be possible to improve the efficacy of ICI therapies through further modulation of the suppressive tumor immune microenvironment (TIME). Several factors may limit immune response in TNBC including aberrant growth factor signaling, such as VEGFR2 and cMet signaling, inefficient vascularization, poor delivery of drugs and immune cells, and the skewing of immune cell populations toward immunosuppressive phenotypes. Here we investigate the immune-modulating properties of AXT201, a novel 20 amino-acid integrin-binding peptide in two syngeneic mouse TNBC models: 4T1-BALB/c and NT4-FVB. AXT201 treatment improved survival in the NT4 model by 20% and inhibited the growth of 4T1 tumors by 47% over 22 days postinoculation. Subsequent immunohistochemical analyses of 4T1 tumors also showed a 53% reduction in vascular density and a 184% increase in pericyte coverage following peptide treatment. Flow cytometry analyses demonstrated evidence of a more favorable anti-tumor immune microenvironment following treatment with AXT201, including significant decreases in the populations of T regulatory cells, monocytic myeloid-derived suppressor cells, and PD-L1 expressing cells and increased expression of T cell functional markers. Together, these findings demonstrate immune-activating properties of AXT201 that could be developed in combination with other immunomodulatory agents in the treatment of TNBC.

show abstract

Section: Discussionmentioning

confidence: 99%

Regulation of the tumor immune microenvironment and vascular normalization in TNBC murine models by a novel peptide

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Integrin αvβ3 is another receptor involved, in melanoma context, in immunotherapy resistance through its regulation of the PDL-1 expression [ 178 ]. In in vitro and in vivo melanoma models, several evidences showed that integrin αvβ3 promotes the expression of PDL-1 through activation of STAT1 [ 179 ].…”

Section: Tme Implications In Drug Resistance For Melanomamentioning

confidence: 99%

Tumor Microenvironment: Implications in Melanoma Resistance to Targeted Therapy and Immunotherapy

Falcone

Cognetti

Bazzichetto

et al. 2020

Cancers

View full text Add to dashboard Cite

Antitumor therapies have made great strides in recent decades. Chemotherapy, aggressive and unable to discriminate cancer from healthy cells, has given way to personalized treatments that, recognizing and blocking specific molecular targets, have paved the way for targeted and effective therapies. Melanoma was one of the first tumor types to benefit from this new care frontier by introducing specific inhibitors for v-Raf murine sarcoma viral oncogene homolog B (BRAF), mitogen-activated protein kinase kinase (MEK), v-kit Hardy–Zuckerman 4 feline sarcoma viral oncogene homolog (KIT), and, recently, immunotherapy. However, despite the progress made in the melanoma treatment, primary and/or acquired drug resistance remains an unresolved problem. The molecular dynamics that promote this phenomenon are very complex but several studies have shown that the tumor microenvironment (TME) plays, certainly, a key role. In this review, we will describe the new melanoma treatment approaches and we will analyze the mechanisms by which TME promotes resistance to targeted therapy and immunotherapy.

show abstract

“…Increases tumor progression [47] Increases lymph node metastasis [48] Increases bone metastasis [49] Is involved in cancer immune evasion [50] Glioma [51] Vitronectin Head and neck cancer [40] Fibrinogen Non-small cell lung cancer [52] Osteopontin…”

Section: Fibronectinmentioning

confidence: 99%

Targeting Integrins in Cancer Nanomedicine: Applications in Cancer Diagnosis and Therapy

Opadele

Onodera

et al. 2019

Cancers

View full text Add to dashboard Cite

Due to advancements in nanotechnology, the application of nanosized materials (nanomaterials) in cancer diagnostics and therapeutics has become a leading area in cancer research. The decoration of nanomaterial surfaces with biological ligands is a major strategy for directing the actions of nanomaterials specifically to cancer cells. These ligands can bind to specific receptors on the cell surface and enable nanomaterials to actively target cancer cells. Integrins are one of the cell surface receptors that regulate the communication between cells and their microenvironment. Several integrins are overexpressed in many types of cancer cells and the tumor microvasculature and function in the mediation of various cellular events. Therefore, the surface modification of nanomaterials with integrin-specific ligands not only increases their binding affinity to cancer cells but also enhances the cellular uptake of nanomaterials through the intracellular trafficking of integrins. Moreover, the integrin-specific ligands themselves interfere with cancer migration and invasion by interacting with integrins, and this finding provides a novel direction for new treatment approaches in cancer nanomedicine. This article reviews the integrin-specific ligands that have been used in cancer nanomedicine and provides an overview of the recent progress in cancer diagnostics and therapeutic strategies involving the use of integrin-targeted nanomaterials.

show abstract

αvβ3-integrin regulates PD-L1 expression and is involved in cancer immune evasion

Cited by 57 publications

References 55 publications

Regulation of the tumor immune microenvironment and vascular normalization in TNBC murine models by a novel peptide

Regulation of the tumor immune microenvironment and vascular normalization in TNBC murine models by a novel peptide

Tumor Microenvironment: Implications in Melanoma Resistance to Targeted Therapy and Immunotherapy

Targeting Integrins in Cancer Nanomedicine: Applications in Cancer Diagnosis and Therapy

Contact Info

Product

Resources

About