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Temozolomide-based therapy may remodel the tumor microenvironment and enhance immunotherapy sensitivity in advanced
Huijing Tan1, Zhuo Li2, Jianguo Zhou3
1Department of Medical Oncology.
Abstract:
Leiomyosarcoma (LMS) is characterized by inherent resistance to immune checkpoint blockade, with no conclusive evidence supporting the efficacy of programmed death-1 (PD-1)/programmed death-ligand 1 inhibitor, and it is generally classified as a nonimmunogenic sarcoma subtype. This study analyzed the therapeutic efficacy of temozolomide (TEM)-based regimens in patients with advanced LMS and evaluated pathological changes after TEM treatment to explore the potential role of immunotherapies and the mechanisms that could enhance immunotherapy sensitivity after TEM treatment. This retrospective review included patients with advanced LMS treated at the Cancer Hospital, Chinese Academy of Medical Sciences, and Peking Union Medical College. All patients initiated TEM-based treatments between September 2018 and December 2024. We evaluated patients with advanced LMS and available pathological data before and after TEM-based therapy and those who received subsequent immunotherapy. In total, 47 patients received anthracycline combined with TEM, and 18 patients received gemcitabine combined with TEM. Overall median progression-free survival (mPFS) was 10.0 months, whereas median overall survival (mOS) was 31.0 months. Among six patients who received subsequent PD-1-based immunotherapy after TEM-containing regimens, mPFS and mOS were 13.0 and 45.0 months, respectively. O6-methylguanine DNA methyltransferase negativity tended to be associated with improved survival. Post-TEM biopsies revealed dynamic changes in mismatch repair gene expression, tertiary lymphoid structure counts, and the combined positive score. TEM-based regimens are effective for advanced LMS. Furthermore, pathological changes observed after TEM treatment suggest potential modulation of the tumor microenvironment, supporting further investigation into the integration of immunotherapies in this setting.
Insights
Temozolomide-based regimens show efficacy in advanced leiomyosarcoma (LMS), improving progression-free survival. Post-treatment analysis suggests potential for combining temozolomide with immunotherapy to enhance treatment outcomes in LMS.
Area of Science:
- Oncology
- Medical Research
- Sarcoma Treatment
Background:
- Leiomyosarcoma (LMS) is typically resistant to immune checkpoint blockade therapies.
- LMS is often considered a nonimmunogenic sarcoma subtype, limiting immunotherapy options.
- Investigating novel therapeutic strategies for advanced LMS is crucial.
Purpose of the Study:
- To evaluate the efficacy of temozolomide (TEM)-based regimens in advanced LMS patients.
- To analyze pathological changes post-TEM treatment to understand potential immunotherapy enhancement.
- To explore mechanisms of increased immunotherapy sensitivity after TEM therapy.
Main Methods:
- Retrospective review of advanced LMS patients treated with TEM-based regimens.
- Analysis of pathological data before and after TEM treatment.
- Evaluation of patients receiving subsequent programmed death-1 (PD-1) inhibitor immunotherapy.
Main Results:
- TEM-based regimens demonstrated a median progression-free survival (mPFS) of 10.0 months and median overall survival (mOS) of 31.0 months.
- Patients receiving subsequent PD-1 immunotherapy after TEM showed improved outcomes (mPFS: 13.0 months, mOS: 45.0 months).
- Post-TEM biopsies indicated dynamic changes in tumor microenvironment markers, including mismatch repair gene expression and tertiary lymphoid structures.
Conclusions:
- TEM-based regimens are effective for advanced LMS.
- TEM treatment may modulate the tumor microenvironment, potentially enhancing immunotherapy sensitivity.
- Combination strategies involving TEM and immunotherapy warrant further investigation for LMS treatment.
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