Basis for Immunotherapy for Treatment of Meningiomas

Abstract

Meningiomas are common tumors that account for approximately one third of CNS tumors diagnosed every year. They are classified by the World Health Organization in grades I-III. Higher grades have an increased rate of growth, invasiveness, rate of recurrence, and worse outcomes than lower grades. Most meningiomas are grade I, while ~18% of meningiomas are grade II and III in hospital-based series. Meningiomas are typically “benign” tumors that are treated with surgery and radiation. However, when they recur or are unresectable, treatment options are very limited, especially since they are chemotherapy-resistant. Recent advances in the treatment of cancers with immunotherapy have focused on checkpoint blockade as well as other types of immunotherapy. There is emerging evidence supporting the use of immunotherapy as a potentially effective treatment strategy for meningioma patients. The immune microenvironment of meningiomas is a complex interplay of genetic alterations, immunomodulatory protein expression, and tumor-immune cell interactions. Meningiomas are known to be infiltrated by immune cells including microglia, macrophages, B-cells, and T-cells. Several mechanisms contribute to decreased an ti-tumor immune response, allowing tumor growth and evasion of the immune system. We discuss the most current knowledge on the immune micro-environment of meningiomas, preclinical findings of immunotherapy in meningiomas, meningioma immunotherapy clinical trials, and also offer insight into future prospects for immunotherapies in meningiomas.

M2-Macrophage-Derived Exosomes Promote Meningioma Progression through TGF-β Signaling Pathway

“…Despite improvements in the treatment of meningiomas over the past decade, the role of the TME in meningioma development remains unclear. Previous studies have suggested that a variety of stromal cells, including TAMs, interact with tumor cells in the TME, which contributes to tumor progression [ 14 , 15 , 17 ]. However, the molecular mechanisms underlying the integral role of infiltrating TAMs in the development of malignant meningiomas have not been fully studied.…”

“…Unlike M1 TAMs, which secrete proinflammatory factors (TNF α , IL-6, and IL-12), M2 TAMs are known to be anti-inflammatory-activated macrophages and can contribute to angiogenesis and tumor growth by regulating intercellular communication in the TME [ 11 – 13 ]. Meningioma is not restricted by the blood-brain barrier, which allows it to come into contact with peripheral immune cells more frequently [ 14 , 15 ]. Several studies have shown that TAMs are enriched in meningioma tissue as a major immune cell population [ 16 – 18 ].…”

Proliferative Potential, and Inflammatory Tumor Microenvironment in Meningioma Correlate with Neurological Function at Presentation and Anatomical Location—From Convexity to Skull Base and Spine

“…PD-L1 expressing tumor cells might act in an inhibitory way on the activation of T-cells by binding to the PD-1 surface receptor of both T- and B-Cells [ 73 ]. Against this backdrop, there are several ongoing prospective trials analyzing the anti-PD1 antibodies avelumab, nivolumab, or pembrolizumab as new treatment options for meningiomas [ 74 ]. However, it must be remembered that CD68 staining does not enable a differentiation of the macrophage phenotypes.…”

The Long and Winding Road: An Overview of the Immunological Landscape of Intracranial Meningiomas

“…Mostly recently, due to new information, this classification was theoretically reconsidered, and new concepts like peritumoral immune cell infiltration have developed. Human tumors are generally characterized by the presence of infiltrated immune cells that have a documented role in conditioning tumor recurrence and oncological progression [ 5 ]; it is well-known that the tumor microenvironment represents the ecosystem that provides support for oncological cells to grow, and immune cells can be actors in both reducing the oncological cells’ growth and providing support in tumor feeding [ 6 ]. These observations lead to the concept of “immune surveillance”, and to the study of the peritumoral environment in order to tailor a rescue therapy when surgery cannot be considered an option for the patient [ 7 ].…”

“…Considering extra-assial lesions, migration to the meningioma microenvironment is even easier [ 6 , 8 ]. To date, the mainstay of meningioma treatment has been represented by surgery and/or radiotherapy [ 9 ], but the role of immunotherapy is gaining more attention in the neuro-oncological field, along with the recent findings mentioned above, and with medical and prognostic progress in body tumor treatment [ 5 , 10 , 11 ].…”