Is the Deciduoid Variant of Pleural Mesothelioma Significant?

Aujayeb, Avinash; Taylor, Leah

doi:10.1016/j.jtho.2020.02.031

Cited by 1 publication

(1 citation statement)

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“…Epithelioid MPM is the most common and favorable subtype, although patients’ median survival is only 13 months after diagnosis [ 5 ]. The sarcomatoid is the rarest and most aggressive subtype, does not benefit from surgery, and has a median survival of 4 months, despite chemotherapy [ 6 ]. The biphasic is characterized by a mixed population of square-shaped (epithelioid) with elongated and spindle-shaped (sarcomatoid) cells; it accounts for 10–15% of MPM cases and has an intermediate prognosis that lies between the other two subtypes (median survival of 8 months) and might be linked with the proportion of the sarcomatoid component [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

Inhibition of the Histone Methyltransferase EZH2 Enhances Protumor Monocyte Recruitment in Human Mesothelioma Spheroids

Mola

Pinton

Erreni

et al. 2021

IJMS

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Malignant pleural mesothelioma (MPM) is a highly aggressive cancer with a long latency period and dismal prognosis. Recently, tazemetostat (EPZ-6438), an inhibitor of the histone methyltransferase EZH2, has entered clinical trials due to the antiproliferative effects reported on MPM cells. However, the direct and indirect effects of epigenetic reprogramming on the tumor microenvironment are hitherto unexplored. To investigate the impact of tumor-associated macrophages (TAMs) on MPM cell responsiveness to tazemetostat, we developed a three-dimensional MPM spheroid model that recapitulates in vitro, both monocytes’ recruitment in tumors and their functional differentiation toward a TAM-like phenotype (Mo-TAMs). Along with an increased expression of genes for monocyte chemoattractants, inhibitory immune checkpoints, immunosuppressive and M2-like molecules, Mo-TAMs promote tumor cell proliferation and spreading. Prolonged treatment of MPM spheroids with tazemetostat enhances both the recruitment of Mo-TAMs and the expression of their protumor phenotype. Therefore, Mo-TAMs profoundly suppress the antiproliferative effects due to EZH2 inhibition in MPM cells. Overall, our findings indicate that TAMs are a driving force for MPM growth, progression, and resistance to tazemetostat; therefore, strategies of TAM depletion might be evaluated to improve the therapeutic efficacy of pharmacological inhibition of EZH2.

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Section: Introductionmentioning

confidence: 99%