Markers of T cell infiltration and function associate with favorable outcome in vascularized high-grade serous ovarian carcinoma

Autor: Katelin N. Townsend, Jaeline E. Spowart, Nathan R. West, Julian J. Lum, Hassan Huwait, Michael S. Anglesio, Peter H. Watson, David G. Huntsman, Steve E. Kalloger, Sima Eshragh, Mary A. Elrick
Jazyk: angličtina
Rok vydání: 2013
Předmět:
Adult
Pathology
medicine.medical_specialty
T cell
lcsh:Medicine
CD8-Positive T-Lymphocytes
Poly(A)-Binding Proteins
Granzymes
03 medical and health sciences
Mice
0302 clinical medicine
Lymphocytes
Tumor-Infiltrating
medicine
Autophagy
Biomarkers
Tumor
Cytotoxic T cell
Animals
Humans
lcsh:Science
Aged
Aged
80 and over
Ovarian Neoplasms
Multidisciplinary
biology
Tumor-infiltrating lymphocytes
lcsh:R
FOXP3
Middle Aged
medicine.disease
Survival Analysis
Cell Hypoxia
3. Good health
Cystadenocarcinoma
Serous
T-Cell Intracellular Antigen-1
Granzyme B
Platelet Endothelial Cell Adhesion Molecule-1
medicine.anatomical_structure
Treatment Outcome
Granzyme
030220 oncology & carcinogenesis
biology.protein
Female
lcsh:Q
Neoplasm Grading
Ovarian cancer
CD8
030215 immunology
Research Article
Follow-Up Studies
Zdroj: PLoS ONE, Vol 8, Iss 12, p e82406 (2013)
PLoS ONE
ISSN: 1932-6203
Popis: Background When T cells infiltrate the tumor environment they encounter a myriad of metabolic stressors including hypoxia. Overcoming the limitations imposed by an inadequate tumor vasculature that contributes to these stressors may be a crucial step to immune cells mounting an effective anti-tumor response. We sought to determine whether the functional capacity of tumor infiltrating lymphocytes (TIL) could be influenced by the tumor vasculature and correlated this with survival in patients with ovarian cancer. Methodology and Principal Findings In 196 high-grade serous ovarian tumors, we confirmed that the tumor vascularity as measured by the marker CD31 was associated with improved patient disease-specific survival. We also found that tumors positive for markers of TIL (CD8, CD4 and forkhead box P3 (FoxP3)) and T cell function (granzyme B and T-cell restricted intracellular antigen-1 (TIA-1)) correlated significantly with elevated vascularity. In vitro, hypoxic CD8 T cells showed reduced cytolytic activity, secreted less effector cytokines and upregulated autophagy. Survival analysis revealed that patients had a significant improvement in disease-specific survival when FoxP3 expressing cells were present in CD31-high tumors compared to patients with FoxP3 expressing cells in CD31-low tumors [HR: 2.314 (95% CI 1.049–5.106); p = 0.0377]. Patients with high vascular endothelial growth factor (VEGF) expressing tumors containing granzyme B positive cells had improved survival compared to patients with granzyme B positive cells in VEGF-low tumors [HR: 2.522 (95% CI 1.097–5.799); p = 0.0294]. Significance Overall, this data provides a rationale for developing strategies aimed at improving the adaptability and function of TIL to hypoxic tumor conditions.
Databáze: OpenAIRE
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