Characterization of Circulating and Tumor-infiltrating Immune Cells in Malignant Brain Tumors

Brain Tumor, Primary Clinical Trial

Official title:

Immunophenotype Characterization of Circulating and Tumor Infiltrating Immune Cells in Malignant Brain Tumors.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05831631
• Other study ID #: NCH 02-2022
• Status: Recruiting
• Start date: August 1, 2022
• Est. completion date: August 1, 2025

Study information

• Verified date: April 2023
• Source: IRCCS San Raffaele
• Contact: Laura Sincinelli
• Phone: 0226435568
• Email: sincinelli.laura[@]hsr.it
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The goal of this observational study is to characterize the circulating leukocyte profile and the immune T cells distribution within the tumor in patients with malignant brain tumors and to correlate these findings with the oncological outcome.

Participants will be subjected to blood sampling before surgery and for 12 months of follow-up. Additional sampling and analysis will be performed on tumor samples.

Description:

High-grade gliomas are the most frequent type of primary brain tumor in adults, and among them, glioblastoma multiforme (GBM) is the most malignant with an associated poor prognosis. Although significant advances have been achieved in GBM biology comprehension, patients' life expectancy is still limited to 18 months.

Brain metastases (BM) are the most frequent neoplasm in the CNS; it is estimated that up to 14% of all newly diagnosed cancers will soon or later metastasize into the brain.

A variety of mechanisms to escape a tumor-specific T cell-mediated immune response have been identified in glioma and other cancer entities.

This project is an observational, prospective, monocentric study on patients candidates for neurosurgical procedures for brain malignant tumors with additional collection of biological material. With the present study, we aim to characterize the phenotype of both circulating- and tumor-infiltrating- immune cells at the diagnosis and their changes during disease progression and after treatment in primary and secondary brain tumors.

Samples will be taken at baseline (before surgery) and at time-points: 3, 6, 9, 12 months

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: August 1, 2025
• Est. primary completion date: July 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion criteria:

• Adult patients (=18 years)

• Able to express informed consent

• With primary or secondary malignant brain tumor

• Requiring neurosurgical treatment (radiosurgery, stereotactic biopsy, surgery)

Exclusion Criteria:

• Patients who do not meet inclusion criteria.

Related Conditions & MeSH terms

• Brain Neoplasms
• Brain Tumor - Metastatic
• Brain Tumor, Primary
• Neoplasms

Intervention

Diagnostic Test:
• Circulating leukocytes immunophenotype
Blood samples will be tested with flow cytometry in order to characterize leukocyte subpopulations and to evaluate the circulating immunophenotype
• Tumor sampling
Immunohistochemical analysis will be performed on tumor samples in order to characterize immune T cells distribution within the tumor.

Locations

Country	Name	City	State
Italy	IRCCS San Raffaele Scientific Institute	Milan

Sponsors (1)

Lead Sponsor	Collaborator
Pietro Mortini, MD, Prof.

Country where clinical trial is conducted

Italy, 

References & Publications (14)

Barnholtz-Sloan JS, Sloan AE, Davis FG, Vigneau FD, Lai P, Sawaya RE. Incidence proportions of brain metastases in patients diagnosed (1973 to 2001) in the Metropolitan Detroit Cancer Surveillance System. J Clin Oncol. 2004 Jul 15;22(14):2865-72. doi: 10.1200/JCO.2004.12.149. — View Citation

Gagliardi F, De Domenico P, Snider S, Roncelli F, Pompeo E, Barzaghi LR, Bulotta A, Gregorc V, Lazzari C, Cascinu S, Finocchiaro G, Mortini P. Role of stereotactic radiosurgery for the treatment of brain metastasis in the era of immunotherapy: A systematic review on current evidences and predicting factors. Crit Rev Oncol Hematol. 2021 Sep;165:103431. doi: 10.1016/j.critrevonc.2021.103431. Epub 2021 Jul 27. — View Citation

Kim YH, Jung TY, Jung S, Jang WY, Moon KS, Kim IY, Lee MC, Lee JJ. Tumour-infiltrating T-cell subpopulations in glioblastomas. Br J Neurosurg. 2012 Feb;26(1):21-7. doi: 10.3109/02688697.2011.584986. Epub 2011 Jun 27. — View Citation

Kmiecik J, Poli A, Brons NH, Waha A, Eide GE, Enger PO, Zimmer J, Chekenya M. Elevated CD3+ and CD8+ tumor-infiltrating immune cells correlate with prolonged survival in glioblastoma patients despite integrated immunosuppressive mechanisms in the tumor microenvironment and at the systemic level. J Neuroimmunol. 2013 Nov 15;264(1-2):71-83. doi: 10.1016/j.jneuroim.2013.08.013. Epub 2013 Aug 31. — View Citation

Kromer C, Xu J, Ostrom QT, Gittleman H, Kruchko C, Sawaya R, Barnholtz-Sloan JS. Estimating the annual frequency of synchronous brain metastasis in the United States 2010-2013: a population-based study. J Neurooncol. 2017 Aug;134(1):55-64. doi: 10.1007/s11060-017-2516-7. Epub 2017 May 31. — View Citation

Lohr J, Ratliff T, Huppertz A, Ge Y, Dictus C, Ahmadi R, Grau S, Hiraoka N, Eckstein V, Ecker RC, Korff T, von Deimling A, Unterberg A, Beckhove P, Herold-Mende C. Effector T-cell infiltration positively impacts survival of glioblastoma patients and is impaired by tumor-derived TGF-beta. Clin Cancer Res. 2011 Jul 1;17(13):4296-308. doi: 10.1158/1078-0432.CCR-10-2557. Epub 2011 Apr 8. — View Citation

Lowery FJ, Yu D. Brain metastasis: Unique challenges and open opportunities. Biochim Biophys Acta Rev Cancer. 2017 Jan;1867(1):49-57. doi: 10.1016/j.bbcan.2016.12.001. Epub 2016 Dec 6. — View Citation

Mauldin IS, Jo J, Wages NA, Yogendran LV, Mahmutovic A, Young SJ, Lopes MB, Slingluff CL Jr, Erickson LD, Fadul CE. Proliferating CD8+ T Cell Infiltrates Are Associated with Improved Survival in Glioblastoma. Cells. 2021 Dec 1;10(12):3378. doi: 10.3390/cells10123378. — View Citation

Mohme M, Schliffke S, Maire CL, Runger A, Glau L, Mende KC, Matschke J, Gehbauer C, Akyuz N, Zapf S, Holz M, Schaper M, Martens T, Schmidt NO, Peine S, Westphal M, Binder M, Tolosa E, Lamszus K. Immunophenotyping of Newly Diagnosed and Recurrent Glioblastoma Defines Distinct Immune Exhaustion Profiles in Peripheral and Tumor-infiltrating Lymphocytes. Clin Cancer Res. 2018 Sep 1;24(17):4187-4200. doi: 10.1158/1078-0432.CCR-17-2617. Epub 2018 Feb 14. — View Citation

Olar A, Aldape KD. Using the molecular classification of glioblastoma to inform personalized treatment. J Pathol. 2014 Jan;232(2):165-77. doi: 10.1002/path.4282. — View Citation

Sayour EJ, McLendon P, McLendon R, De Leon G, Reynolds R, Kresak J, Sampson JH, Mitchell DA. Increased proportion of FoxP3+ regulatory T cells in tumor infiltrating lymphocytes is associated with tumor recurrence and reduced survival in patients with glioblastoma. Cancer Immunol Immunother. 2015 Apr;64(4):419-27. doi: 10.1007/s00262-014-1651-7. Epub 2015 Jan 3. — View Citation

Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U, Curschmann J, Janzer RC, Ludwin SK, Gorlia T, Allgeier A, Lacombe D, Cairncross JG, Eisenhauer E, Mirimanoff RO; European Organisation for Research and Treatment of Cancer Brain Tumor and Radiotherapy Groups; National Cancer Institute of Canada Clinical Trials Group. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005 Mar 10;352(10):987-96. doi: 10.1056/NEJMoa043330. — View Citation

Vilarino N, Bruna J, Bosch-Barrera J, Valiente M, Nadal E. Immunotherapy in NSCLC patients with brain metastases. Understanding brain tumor microenvironment and dissecting outcomes from immune checkpoint blockade in the clinic. Cancer Treat Rev. 2020 Sep;89:102067. doi: 10.1016/j.ctrv.2020.102067. Epub 2020 Jul 7. — View Citation

Wang W, Shi G, Ma B, Hao X, Dong X, Zhang B. Chemotherapy for Adults with Malignant Glioma: A Systematic Review and Network Meta-Analysis. Turk Neurosurg. 2017;27(2):174-181. doi: 10.5137/1019-5149.JTN.15462-15.0. — View Citation

* Note: There are 14 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Baseline leucocytes count	Leucocytes count (10^3/ml), total lymphocytes count (10^3/ml)	Baseline
Primary	Baseline leucocytes immunophenotype	Determination of different leucocyte subpopulations (%)	Baseline
Primary	Baseline tumor-infiltrating lymphocytes count	Infiltrating lymphocytes count (10^3/ml)	After surgery (tumor sampling)
Primary	Baseline tumor-infiltrating leucocytes immunophenotype	Infiltrating T-cell subpopulations (%)	After surgery (tumor sampling)