Astrocytomas include a wide range of tumors with unique mutations and varying grades of malignancy. These tumors all originate from the astrocyte, a star-shaped glial cell that plays a major role in supporting functions of the central nervous system (CNS), including blood-brain barrier (BBB) development and maintenance, water and ion regulation, influencing neuronal synaptogenesis, and stimulating the immunological response. In terms of epidemiology, glioblastoma (GB), the most common and malignant astrocytoma, generally occur with higher rates in Australia, Western Europe, and Canada, with the lowest rates in Southeast Asia. Additionally, significantly higher rates of GB are observed in males and non-Hispanic whites. It has been suggested that higher levels of testosterone observed in biological males may account for the increased rates of GB. Hereditary syndromes such as Cowden, Lynch, Turcot, Li-Fraumeni, and neurofibromatosis type 1 have been linked to increased rates of astrocytoma development. While there are a number of specific gene mutations that may influence malignancy or be targeted in astrocytoma treatment, O6-methylguanine-DNA methyltransferase (MGMT) gene function is an important predictor of astrocytoma response to chemotherapeutic agent temozolomide (TMZ). TMZ for primary and bevacizumab in the setting of recurrent tumor formation are two of the main chemotherapeutic agents currently approved in the treatment of astrocytomas. While stereotactic radiosurgery (SRS) has debatable implications for increased survival in comparison to whole-brain radiotherapy (WBRT), SRS demonstrates increased precision with reduced radiation toxicity. When considering surgical resection of astrocytoma, the extent of resection (EoR) is taken into consideration. Subtotal resection (STR) spares the margins of the T1 enhanced magnetic resonance imaging (MRI) region, gross total resection (GTR) includes the margins, and supramaximal resection (SMR) extends beyond the margin of the T1 and into the T2 region. Surgical resection, radiation, and chemotherapy are integral components of astrocytoma treatment.

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Background: Glioblastoma (GBM) is an aggressive brain cancer infiltrated by immunosuppressive myeloid-derived suppressor cells (MDSCs) and confers poor prognosis. To address this, our group developed an adoptive cellular therapy platform specifically for primary central nervous system (CNS) malignancies that yielded significant survival benefits against multiple brain cancer models. Preclinically, this platform establishes proof-of-concept for lymphodepletion achieved through host conditioning with total body irradiation (TBI). While host conditioning is thought to remove immunosuppressive elements, the aim of this study was to determine how immune recovery is affected by adoptive cellular therapy. Methods: The adoptive cellular therapy platform includes myeloablative TBI, hematopoietic stem cell rescue, tumor-specific T cells, and dendritic cell vaccines. KR158B glioma-bearing mice were treated with adoptive cellular therapy and secondary lymphoid organs were evaluated using flow cytometry, spatial genomics, and multiplex protein analysis. Single-cell transcriptomics and trans-well migration assay evaluated the role of CCL12 on MDSC migration. Results: We show that adoptive cellular therapy allows for reconstitution of MDSC and tumor-associated macrophages in secondary lymphoid organs but prevents their accumulation in the tumor microenvironment (TME). This allows for the increased engraftment and activation of T cells within the TME. Next, we show that adoptive cellular therapy decreases CCL12 in the TME and neutralization of TAM-derived CCL12 in vitro inhibits MDSC migration in glioma. Conclusion: These findings suggest a previously unrecognized association between both loss of intratumoral immunosuppressive elements after immunotherapy and TAM-derived CCL12, a chemokine that promotes MDSC migration. Future in vivo studies will evaluate the causal role of CCL12 on MDSC recruitment in glioma.

Background/Objectives: Glioblastoma (GBM) remains a lethal primary CNS malignancy with limited response to immunotherapy. Adoptive cellular therapy (ACT) improves survival in preclinical models, yet tumors ultimately recur. While T cell exhaustion is a common mechanism of resistance, the contribution of dendritic cell (DC) dysfunction remains unclear. We aimed to define mechanisms of immune escape following ACT, focusing on DC function and the role of hypoxia. Methods: Using a murine glioma model (KR158B), mice were treated with ACT consisting of tumor RNA–pulsed DC vaccines and adoptively transferred T cells. Tumor-infiltrating immune populations were analyzed by flow cytometry. DC function was assessed using T cell activation assays. Bulk RNA sequencing and gene set enrichment analysis were performed on sorted DCs. Hypoxia was modeled in vitro, and HIF1α was perturbed using CRISPR-mediated knockout. Results: ACT significantly increased survival but did not prevent tumor recurrence. Escaped tumors contained abundant cytotoxic, non-exhausted T cells, indicating that T cell dysfunction was not the primary driver of resistance. Instead, tumor-associated DCs exhibited impaired T cell activation despite preserved antigen uptake. Transcriptomic analyses revealed reduced antigen presentation and co-stimulatory signaling, alongside increased expression of tolerogenic factors. ACT-treated tumors demonstrated heightened hypoxia pathway activation, with elevated HIF1α expression in DCs. Hypoxia induced DC tolerogenic programs and reduced their ability to activate T cells, an effect partially reversed by HIF1α disruption. Increased immune infiltration and inflammation following ACT further amplified hypoxia signaling. Conclusions: DC dysfunction is a key mechanism of immune escape following ACT in glioma. Hypoxia-driven tolerization of DCs impairs sustained anti-tumor immunity, highlighting the hypoxia–DC axis as a promising therapeutic target to enhance immunotherapy efficacy.

Case: A 29-year-old woman with acute peroneal tendon subluxation underwent superior retinacular repair. On exposure, a single peroneal myotendinous unit was encountered, as opposed to the usual presence of independent peroneal tendons arising from separate muscle bellies. At 3-year follow-up, she has had no recurrence with full return to activity and no limitations. Conclusion: Multiple peroneal myotendinous variants have been described; however, this report is the first to describe direct intraoperative observation of a single peroneal myotendinous unit. Whether this anatomic variant contributed to the patient’s problem or has other potential clinical sequelae remains to be elucidated.