Affiliation:
1. The Cancer Immunotherapy Laboratory, The Tel-Aviv Sourasky Medical Center , Tel-Aviv , Israel
2. Neurosurgery Department, The Tel-Aviv Sourasky Medical Center , Tel-Aviv , Israel
3. Oncology Department, The Tel-Aviv Sourasky Medical Center , Tel-Aviv , Israel
Abstract
Abstract
Background
GBM is an aggressive grade 4 primary brain tumor (BT), with a 5%–13% 5-year survival. Most human GBMs manifest as immunologically “cold” tumors or “immune deserts,” yet the promoting or suppressive roles of specific lymphocytes within the GBM tumor microenvironment (TME) is of considerable debate.
Methods
We used meticulous multiparametric flow cytometry (FC) to determine the lymphocytic frequencies in 102 GBMs, lower-grade gliomas, brain metastases, and nontumorous brain specimen. FC-attained frequencies were compared with frequencies estimated by “digital cytometry.” The FC-derived data were combined with the patients’ demographic, clinical, molecular, histopathological, radiological, and survival data.
Results
Comparison of FC-derived data to CIBERSORT-estimated data revealed the poor capacity of digital cytometry to estimate cell frequencies below 0.2%, the frequency range of most immune cells in BTs. Isocitrate dehydrogenase (IDH) mutation status was found to affect TME composition more than the gliomas’ pathological grade. Combining FC and survival data disclosed that unlike other cancer types, the frequency of helper T cells (Th) and cytotoxic T lymphocytes (CTL) correlated negatively with glioma survival. In contrast, the frequencies of γδ-T cells and CD56bright natural killer cells correlated positively with survival. A composite parameter combining the frequencies of these 4 tumoral lymphocytes separated the survival curves of GBM patients with a median difference of 10 months (FC-derived data; P < .0001, discovery cohort), or 4.1 months (CIBERSORT-estimated data; P = .01, validation cohort).
Conclusions
The frequencies of 4 TME lymphocytes strongly correlate with the survival of patients with GBM, a tumor considered an immune desert.
Funder
Israeli ministry of health
Publisher
Oxford University Press (OUP)
Subject
Cancer Research,Neurology (clinical),Oncology
Cited by
6 articles.
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