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

NCT05831631 | Recruiting

• 1 other identifier: NCH 02-2022
• Study Type: observational
• Target: 200
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Brain Tumor, Primary; Brain Tumor - Metastatic

Keywords

Immunophenotype; Primary and secondary brain tumor

Outcome Measures

Primary Outcomes (4)

• Baseline leucocytes count

  Leucocytes count (10\^3/ml), total lymphocytes count (10\^3/ml)

  Baseline

• Baseline leucocytes immunophenotype

  Determination of different leucocyte subpopulations (%)

  Baseline

• Baseline tumor-infiltrating lymphocytes count

  Infiltrating lymphocytes count (10\^3/ml)

  After surgery (tumor sampling)

• Baseline tumor-infiltrating leucocytes immunophenotype

  Infiltrating T-cell subpopulations (%)

  After surgery (tumor sampling)

Study Arms (1)

Included patients

The study population will comprise 200 (two hundred) adult patients candidate to neurosurgical treatment for newly diagnosed malignant brain tumors, able to express an informed consent.

Diagnostic Test: Circulating leukocytes immunophenotype; Diagnostic Test: Tumor sampling

Interventions

Circulating leukocytes immunophenotype DIAGNOSTIC_TEST

Blood samples will be tested with flow cytometry in order to characterize leukocyte subpopulations and to evaluate the circulating immunophenotype

Included patients

Tumor sampling DIAGNOSTIC_TEST

Immunohistochemical analysis will be performed on tumor samples in order to characterize immune T cells distribution within the tumor.

Included patients

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Adult patients with a diagnosis of malignant brain tumor (primary or secondary) and meeting the criteria for undergoing neurosurgical treatment (radiosurgery, stereotactic biopsy, surgery).

You may qualify if:

• Adult patients (≥18 years)
• Able to express informed consent
• With primary or secondary malignant brain tumor
• Requiring neurosurgical treatment (radiosurgery, stereotactic biopsy, surgery)

Sponsors & Collaborators

• Pietro Mortini, MD, Prof.: lead

Study Sites (1)

IRCCS San Raffaele Scientific Institute

Milan, Milan, 20132, Italy

RECRUITING

Related Publications (14)

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  PMID: 27939792 BACKGROUND

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  PMID: 28567587 BACKGROUND

• 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.

  PMID: 21707245 BACKGROUND

• 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.

  PMID: 21478334 BACKGROUND

• 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.

  PMID: 24045166 BACKGROUND

• 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.

  PMID: 25555571 BACKGROUND

• 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.

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• 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.

  PMID: 29444930 BACKGROUND

• 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.

  PMID: 34324961 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Blood samples for lymphocyte extraction and immunophenotype detection.

MeSH Terms

Conditions

Brain Neoplasms

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Study Officials

• Pietro Mortini, MD, Prof.

  IRCCS San Raffaele Scientific Institute

  STUDY DIRECTOR

Central Study Contacts

Laura Sincinelli

CONTACT

0226435568; sincinelli.laura@hsr.it

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: March 16, 2023
• First Posted: April 26, 2023
• Study Start: August 1, 2022
• Primary Completion (Estimated): July 31, 2028
• Study Completion (Estimated): August 1, 2029
• Last Updated: June 11, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)