Chemotherapy of Malignant Pleural Mesothelioma Does not Preclude Use of Check-Point Blockade

Curioni-Fontecedro, Alessandra; Cecconi, Virginia; Bosco, Enrico; Schmitt-Opitz, Isabelle; Weder, Walter; Stahel, R.; Broek, M. van den; Tischler, Verena

doi:10.1093/annonc/mdv052.01

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“…Binding of ICOS-L to OPN, instead promoted tumor metastases in a mouse breast cancer model (85). ICOS-L is expressed also in human malignant mesothelioma (87). Thus, also for this new molecular partner of OPN, interfering with this binding may be explored as a new therapeutic approach.…”

Section: Icos a Costimulatory Receptor Expressed On Activated T (86)mentioning

confidence: 99%

Important functional role of the protein osteopontin in the progression of malignant pleural mesothelioma

et al. 2023

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BackgroundMalignant Pleural Mesothelioma (MPM) is an aggressive cancer of the mesothelial lining associated with exposure to airborne non-degradable asbestos fibers. Its poor response to currently available treatments prompted us to explore the biological mechanisms involved in its progression. MPM is characterized by chronic non-resolving inflammation; in this study we investigated which inflammatory mediators are mostly expressed in biological tumor samples from MPM patients, with a focus on inflammatory cytokines, chemokines and matrix components.MethodsExpression and quantification of Osteopontin (OPN) was detected in tumor and plasma samples of MPM patients by mRNA, immunohistochemistry and ELISA. The functional role of OPN was investigated in mouse MPM cell lines in vivo using an orthotopic syngeneic mouse model.ResultsIn patients with MPM, the protein OPN was significantly more expressed in tumors than in normal pleural tissues and predominantly produced by mesothelioma cells; plasma levels were elevated in patients and associated with poor prognosis. However, modulation of OPN levels was not significantly different in a series of 18 MPM patients receiving immunotherapy with durvalumab alone or with pembrolizumab in combination with chemotherapy, some of whom achieved a partial clinical response. Two established murine mesothelioma cell lines: AB1 and AB22 of sarcomatoid and epithelioid histology, respectively, spontaneously produced high levels of OPN. Silencing of the OPN gene (Spp1) dramatically inhibited tumor growth in vivo in an orthotopic model, indicating that OPN has an important promoting role in the proliferation of MPM cells. Treatment of mice with anti-CD44 mAb, blocking a major OPN receptor, significantly reduced tumor growth in vivo.ConclusionThese results demonstrate that OPN is an endogenous growth factor for mesothelial cells and inhibition of its signaling may be helpful to restrain tumor progression in vivo. These findings have translational potential to improve the therapeutic response of human MPM.

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Section: Icos a Costimulatory Receptor Expressed On Activated T (86)mentioning

confidence: 99%

Important functional role of the protein osteopontin in the progression of malignant pleural mesothelioma

et al. 2023

View full text Add to dashboard Cite

show abstract

Chemotherapy of Malignant Pleural Mesothelioma Does not Preclude Use of Check-Point Blockade

Cited by 1 publication

References 0 publications

Important functional role of the protein osteopontin in the progression of malignant pleural mesothelioma

Important functional role of the protein osteopontin in the progression of malignant pleural mesothelioma

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