Background: tumor-infiltrating lymphocytes are prognostic in many human cancers. However, the prognostic value of lymphocytes infiltrating glioblastoma (GBM), and roles in tumor control or progression are unclear. We hypothesized that B and T cell density, and markers of their activity, proliferation, differentiation, or function, would have favorable prognostic significance for patients with GBM.
Methods: initial resection specimens from 77 patients with IDH1/2 wild type GBM who received standard-of-care treatment were evaluated with multiplex immunofluorescence histology (mIFH), for the distribution, density, differentiation, and proliferation of T cells and B cells, as well as for the presence of tertiary lymphoid structures (TLS), and IFNγ expression. Immune infiltrates were evaluated for associations with overall survival (OS) by univariate and multivariate Cox proportional hazards modeling.
Results: in univariate analyses, improved OS was associated with high densities of proliferating (Ki67) CD8 cells (HR 0.36, = 0.001) and CD20 cells (HR 0.51, = 0.008), as well as CD8Tbet cells (HR 0.46, = 0.004), and RORγt cells (HR 0.56, = 0.04). Conversely, IFNγ intensity was associated with diminished OS (HR 0.59, = 0.036). In multivariable analyses, adjusting for clinical variables, including age, resection extent, Karnofsky Performance Status (KPS), and MGMT methylation status, improved OS was associated with high densities of proliferating (Ki67) CD8 cells (HR 0.15, < 0.001), and higher ratios of CD8 cells to CD4 cells (HR 0.31, = 0.005). Diminished OS was associated with increases in patient age (HR 1.21, = 0.005) and higher mean intensities of IFNγ (HR 2.13, = 0.027).
Conclusions: intratumoral densities of proliferating CD8 T cells and higher CD8/CD4 ratios are independent predictors of OS in patients with GBM. Paradoxically, higher mean intensities of IFNγ in the tumors were associated with shorter OS. These findings suggest that survival may be enhanced by increasing proliferation of tumor-reactive CD8 T cells and that approaches may be needed to promote CD8 T cell dominance in GBM, and to interfere with the immunoregulatory effects of IFNγ in the tumor microenvironment.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8699921 | PMC |
http://dx.doi.org/10.3390/cells10123378 | DOI Listing |
Sci Rep
December 2024
Department of Thyroid Surgery, Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China.
Although CCL17 has been reported to exert a vital role in many cancers, the related studies in the thyroid carcinoma have never reported. As a chemokine, CCL17 plays a positive role by promoting the infiltration of immune cells into the tumor microenviroment (TME) to influence tumor invasion and metastasis. Therefore, this study is aimed to investigate the association of CCL17 level with potential prognostic value on tumor immunity in the thyroid carcinoma (THCA) based on the bioinformatics analysis.
View Article and Find Full Text PDFNat Commun
December 2024
State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou, 510060, China.
Aging is associated with increased tumor metastasis and poor prognosis. However, how an aging immune system contributes to the process is unclear. Here, single-cell RNA sequencing reveals that in male mice, aging shifts the lung immune microenvironment towards a premetastatic niche, characterized by an increased proportion of IL-17-expressing γδT (γδ17) and neutrophils.
View Article and Find Full Text PDFNat Commun
December 2024
Drug Hypersensitivity Clinical and Research Center, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan, Taiwan.
Immune checkpoint inhibitors (ICI) represent new anticancer agents and have been used worldwide. However, ICI can potentially induce life-threatening severe cutaneous adverse reaction (SCAR), such as Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), hindering continuous ICI therapy. We examine 6 cohorts including 25 ICI-induced SJS/TEN patients and conduct single-cell RNA sequencing (scRNA-seq) analysis, which shows overexpression of macrophage-derived CXCL10 that recruits CXCR3 cytotoxic T lymphocytes (CTL) in blister cells from ICI-SJS/TEN skin lesions.
View Article and Find Full Text PDFIndian J Med Res
November 2024
Department of Receptor Biology and Tumor Metastasis, Chittaranjan National Cancer Institute, Kolkata, India.
Background & objectives The choice of anesthetic for better perioperative conservation of immune responses has always been contentious. This study investigated the differential impact of the intravenous anesthetic, propofol, and the volatile anesthetic, isoflurane on the T cell immune responses, if any, among individuals going through perioperative breast cancer. Methods Perioperative blood samples (preoperative, intraoperative and postoperative) collected from participants with breast cancer in two arms namely isoflurane arm (n=50) and the propofol arm (n=50) were analyzed for T cell immune response using flow cytometry and ELISA.
View Article and Find Full Text PDFFront Immunol
December 2024
Department of General Pediatrics and Neonatology, Saarland University, Campus Homburg, Homburg, Germany.
Background: The pleural cavity represents a unique immunological compartment that can mount inflammatory reactions during infections, after surgery and in chronic immunological diseases. The connection between systemic immune reactions in the blood and local immune reactions in pleural effusions remains unclear. This study provides the first comprehensive immunological characterization of paired blood and pleural effusion samples, utilizing combined cell and cytokine analyses in pediatric patients undergoing cardiac surgery.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!