Dr Hasanov on Actionable Immune-Resistance Targets in RCC With Brain Metastases

Elshad Hasanov, MD, PhD, medical oncology fellow, The University of Texas MD Anderson Cancer Center, discusses actionable immune-resistance targets in patients with renal cell carcinoma (RCC) with brain metastases.

At the 2023 AACR Annual Meeting, findings were presented on research of the key biological mechanisms that may drive immunosuppressive tumor microenvironments located in brain metastases, apart from the kidney or other metastatic sites. The most notable finding was that neuronal and glial cell infiltration occurred in the microenvironment of brain metastases compared with major cell clusters, Hasanov begins.

Regarding the contribution of neuronal cell and glial cell infiltration in the brain metastasis microenvironment, investigators found that neuronal cells maintain each other through the FGFR2 receptor, Hasanov notes. Moreover, neuronal cells induce the proliferation of the tumor cells through the FGF4 receptor, and they interact with the macrophage B cells and T cells in the brain microenvironment through different ligand receptor interactions, Hasanov adds, noting that previous literature has also suggested that some of these interactions are immune suppressive.

Overall, investigators observed a distinct tumor microenvironment for brain metastases that is driven by the neuronal cell infiltration, Hasanov continues. Investigators expected to observe that the brain metastases had a unique mechanism of immune resistance, Hasanov says. However, at start of the investigation, investigators did not have a pathway in mind to clearly say that this mechanism may be related to T cells, B cells, or macrophages. Using single nucleus RNA sequencing gave investigators an opportunity to identify the neuronal and glial cells, as well as other fibroblasts and macrophages in immune cells to help identify different mechanisms of resistance on each cell type, Hasanov concludes.