Sustained Accumulation of Blood-Derived Macrophages in the Immune Microenvironment of Patients with Recurrent Glioblastoma after Therapy

The cell composition of the glioblastoma (GBM) microenvironment depends on the recruitment of myeloid cells from the blood, promoting tumor progression by inducing immunosuppression. This phenomenon hampers immunotherapies and investigating its complexity may help to tailor new treatments. Peripheral blood and tissue specimens from the central and marginal tumor areas were collected from 44 primary and 19 recurrent GBM patients. Myeloid and lymphoid cell subsets and the levels of immunosuppressive markers were defined by multiparametric flow cytometry. Multiplexed immunohistochemistry was used to confirm the differences in the immune infiltrate and to analyze the cell spatial distribution. Relapsing GBM showed an increased presence of blood-derived macrophages in both tumor areas and a higher frequency of infiltrating lymphocytes, with a high level of exhaustion markers. The expansion of some myeloid-derived suppressor cell (MDSC) subsets in the blood was found in both primary and recurrent GBM patients. A significant inverse correlation between infiltrating T cells and an MDSC subset was also found. In patients with recurrent GBM after standard first-line therapy, the immune-hostile tumor microenvironment and the levels of some MDSC subsets in the blood persisted. Analysis of the immune landscape in GBM relapses aids in the definition of more appropriate stratification and treatment.

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Comparison of Tumor Immune Environment Between Newly Diagnosed and Recurrent Glioblastoma in Matched Patients

10.21203/rs.3.rs-1099110/v1 ◽

2022 ◽

Author(s):

Fei Wang ◽

Sahara J Cathcart ◽

Dominick J DiMaio ◽

Nan Zhao ◽

Jie Chen ◽

...

Keyword(s):

Tumor Infiltrating Lymphocytes ◽

Distribution Patterns ◽

Primary Brain Tumor ◽

Primary Diagnosis ◽

Recurrent Glioblastoma ◽

Initial Diagnosis ◽

Newly Diagnosed ◽

Response To Chemotherapy ◽

Tissue Specimens ◽

Recurrent Gbm

Abstract Purpose: Glioblastoma (GBM) is the most lethal primary brain tumor in adult patients. The disease progression, response to chemotherapy and radiotherapy at initial diagnosis, and prognosis are profoundly associated with the tumor microenvironment (TME), especially the features of tumor-infiltrating immune cells (TII). Recurrent GBM is even more challenging to manage. Differences in the immune environment between newly diagnosed and recurrent GBM and an association with tumor prognosis are not well defined. Methods: To address this knowledge gap, we analyzed the clinical data and tissue specimens from 24 GBM patients (13 at initial diagnosis and 11 at recurrence). The expression levels of multiple immunobiological markers in patients’ GBM at initial diagnosis versus at recurrence were compared, including five patients with both specimens available (paired). The distribution patterns of TII were evaluated in both the intratumoral and perivascular regions. Results: We found that tumors from recurrent GBM have significantly more tumor-infiltrating lymphocytes (TILs) and macrophages and higher PD-L1 expression than tumors at primary diagnosis and benign brain specimens from epilepsy surgery. The pattern changes of the TILs and macrophages of the five paired specimens were consistent with the unpaired patients, while the CD8 to CD4 ratio remained constant from diagnosis to recurrence in the paired tissues. The levels of TILs and macrophages at initial diagnosis did not correlate with OS. TILs and macrophages were increased in recurrent tumors both in intratumoral and perivascular areas, with higher distribution levels in intratumoral than perivascular regions. Higher CD4 or CD8 infiltration at recurrence was associated with worse prognosis, respectively. Conclusion: Our study elucidated that TIL and TAM tend to accumulate in perivascular region and are more abundant in recurrent GBM than newly diagnosed GBM.

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Myeloid-Derived Suppressor Cell Function in Breast Cancer Patients

Case Medical Research ◽

10.31525/ct1-nct04022616 ◽

2019 ◽

Author(s):

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Cell Function ◽

Suppressor Cell ◽

Breast Cancer Patients ◽

Myeloid Derived Suppressor Cell

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Faculty Opinions recommendation of HCV-associated exosomes promote myeloid-derived suppressor cell expansion via inhibiting miR-124 to regulate T follicular cell differentiation and function.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.734020120.793554537 ◽

2018 ◽

Author(s):

Santosh Kumar

Keyword(s):

Cell Differentiation ◽

Cell Expansion ◽

Suppressor Cell ◽

Follicular Cell ◽

Myeloid Derived Suppressor Cell ◽

And Function

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Transcriptomic Analyses of Myeloid-Derived Suppressor Cell Subsets in the Circulation of Colorectal Cancer Patients

Frontiers in Oncology ◽

10.3389/fonc.2020.01530 ◽

2020 ◽

Vol 10 ◽

Author(s):

Varun Sasidharan Nair ◽

Reem Saleh ◽

Salman M. Toor ◽

Nehad M. Alajez ◽

Eyad Elkord

Keyword(s):

Colorectal Cancer ◽

Cancer Patients ◽

Suppressor Cell ◽

Myeloid Derived Suppressor Cell ◽

Colorectal Cancer Patients

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Machine-Learning-Based Radiomics MRI Model for Survival Prediction of Recurrent Glioblastomas Treated with Bevacizumab

Diagnostics ◽

10.3390/diagnostics11071263 ◽

2021 ◽

Vol 11 (7) ◽

pp. 1263

Author(s):

Samy Ammari ◽

Raoul Sallé de Chou ◽

Tarek Assi ◽

Mehdi Touat ◽

Emilie Chouzenoux ◽

...

Keyword(s):

Machine Learning ◽

Therapeutic Option ◽

Binary Classification ◽

Progression Free Survival ◽

Recurrent Glioblastoma ◽

Machine Learning Algorithms ◽

Survival Prediction ◽

Classification Models ◽

Angiogenic Therapy ◽

Recurrent Gbm

Anti-angiogenic therapy with bevacizumab is a widely used therapeutic option for recurrent glioblastoma (GBM). Nevertheless, the therapeutic response remains highly heterogeneous among GBM patients with discordant outcomes. Recent data have shown that radiomics, an advanced recent imaging analysis method, can help to predict both prognosis and therapy in a multitude of solid tumours. The objective of this study was to identify novel biomarkers, extracted from MRI and clinical data, which could predict overall survival (OS) and progression-free survival (PFS) in GBM patients treated with bevacizumab using machine-learning algorithms. In a cohort of 194 recurrent GBM patients (age range 18–80), radiomics data from pre-treatment T2 FLAIR and gadolinium-injected MRI images along with clinical features were analysed. Binary classification models for OS at 9, 12, and 15 months were evaluated. Our classification models successfully stratified the OS. The AUCs were equal to 0.78, 0.85, and 0.76 on the test sets (0.79, 0.82, and 0.87 on the training sets) for the 9-, 12-, and 15-month endpoints, respectively. Regressions yielded a C-index of 0.64 (0.74) for OS and 0.57 (0.69) for PFS. These results suggest that radiomics could assist in the elaboration of a predictive model for treatment selection in recurrent GBM patients.

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Targeting MDSC for Immune-Checkpoint Blockade in Cancer Immunotherapy: Current Progress and New Prospects

Clinical Medicine Insights Oncology ◽

10.1177/11795549211035540 ◽

2021 ◽

Vol 15 ◽

pp. 117955492110355

Author(s):

Tianhang Li ◽

Tianyao Liu ◽

Wenjie Zhu ◽

Shangxun Xie ◽

Zihan Zhao ◽

...

Keyword(s):

Immune Checkpoint ◽

Immune Escape ◽

Suppressor Cell ◽

Immune Checkpoint Blockade ◽

Checkpoint Blockade ◽

Great Promise ◽

Therapy Process ◽

Myeloid Derived Suppressor Cell ◽

Anti Cancer ◽

Immune Suppressor

Immune-checkpoint blockade (ICB) demonstrated inspiring effect and great promise in anti-cancer therapy. However, many obstacles, such as drug resistance and difficulty in patient selection, limited the efficacy of ICB therapy and awaited to be overcome. By timely identification and intervention of the key immune-suppressive promotors in the tumor microenvironment (TME), we may better understand the mechanisms of cancer immune-escape and use novel strategies to enhance the therapeutic effect of ICB. Myeloid-derived suppressor cell (MDSC) is recognized as a major immune suppressor in the TME. In this review, we summarized the roles MDSC played in the cancer context, focusing on its negative biologic functions in ICB therapy, discussed the strategies targeted on MDSC to optimize the diagnosis and therapy process of ICB and improve the efficacy of ICB therapy against malignancies.

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SURG-13. LASER INTERSTITIAL THERMAL THERAPY FOR RECURRENT GLIOBLASTOMA: A REVIEW OF SURVIVAL OUTCOMES COMPARED TO A MATCHED SURGICAL COHORT

Neuro-Oncology ◽

10.1093/neuonc/noaa215.860 ◽

2020 ◽

Vol 22 (Supplement_2) ◽

pp. ii206-ii206

Author(s):

Hassan Fadel ◽

Sameah Haider ◽

Jacob Pawloski ◽

Hesham Zakaria ◽

Farhan Chaudhry ◽

...

Keyword(s):

Surgical Resection ◽

Subgroup Analysis ◽

Tumor Volume ◽

Progression Free Survival ◽

Recurrent Glioblastoma ◽

Thermal Therapy ◽

Survival Outcomes ◽

Repeat Surgery ◽

Laser Interstitial Thermal Therapy ◽

Recurrent Gbm

Abstract INTRODUCTION Glioblastoma (GBM) is uniformly associated with a poor prognosis and inevitable recurrence. Management of recurrent GBM remains unclear, with repeat surgery often employed with varying degrees of success. We evaluated the efficacy of Laser Interstitial Thermal Therapy (LITT) for recurrent GBM when compared to a carefully matched cohort of patients treated with repeat surgical resection. METHODS A retrospective single-institution database was used to identify patients who underwent LITT or surgical resection of recurrent GBM between 2014-2019. LITT patients were matched with surgical resection patients according to baseline demographics, comorbidities, tumor location, and eloquence. Subgroup analysis matching similar patients for tumor volume was also completed. Overall survival (OS) and progression-free survival (PFS) were the primary endpoints. RESULTS A LITT cohort of 20 patients was matched to 50 similar patients who underwent repeat surgical resection. Baseline characteristics were similar between both cohorts apart from tumor volume, which was larger in the surgical cohort (17.5 cc vs. 4.7 cc, p< 0.01). On long-term follow-up, there was no difference in OS (HR, 0.72; 95%CI, 0.36-1.45) or PFS (HR, 0.67; 95%CI, 0.29-1.53) between the LITT and surgical cohorts when controlling for tumor volume. Subgroup analysis of 23 LITT patients matched according to tumor volume with 23 surgical patients with similar clinical characteristics also found no difference in OS (HR, 0.66; 95%CI, 0.33-1.30) or PFS (HR, 0.58; 95%CI, 0.90-1.05) between the cohorts. LITT patients had shorter length of stays (1 vs. 4 days, p< 0.001) and a higher rate of home discharge (84% vs. 67%, p=0.172) compared to the surgical cohort. CONCLUSION After matching for demographic, clinical, and tumor characteristics, there was no difference in outcomes between patients undergoing LITT compared to surgical resection for recurrent GBM. LITT patients had similar survival outcomes yet shorter hospital stays and more favorable dispositions, potentially mitigating post-treatment complications.

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