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OX40 expression enhances the prognostic significance of CD8 positive lymphocyte infiltration in colorectal cancer.
OX40 expression enhances the prognostic significance of CD8 positive lymphocyte infiltration in colorectal cancer.
- Source :
-
Oncotarget [Oncotarget] 2015 Nov 10; Vol. 6 (35), pp. 37588-99. - Publication Year :
- 2015
-
Abstract
- Background: OX40 is a TNF receptor family member expressed by activated T cells. Its triggering by OX40 ligand promotes lymphocyte survival and memory generation. Anti-OX40 agonistic monoclonal antibodies (mAb) are currently being tested in cancer immunotherapy. We explored the prognostic significance of tumor infiltration by OX40+ cells in a large colorectal cancer (CRC) collective.<br />Methods: OX40 gene expression was analyzed in 50 freshly excised CRC and corresponding healthy mucosa by qRT-PCR. A tissue microarray including 657 clinically annotated CRC specimens was stained with anti-OX40, -CD8 and -FOXP3 mAbs by standard immunohistochemistry. The CRC cohort was randomly split into training and validation sets. Correlations between CRC infiltration by OX40+ cells alone, or in combination with CD8+ or FOXP3+ cells, and clinical-pathological data and overall survival were comparatively evaluated.<br />Results: OX40 gene expression in CRC significantly correlated with FOXP3 and CD8 gene expression. High CRC infiltration by OX40+ cells was significantly associated with favorable prognosis in training and validation sets in univariate, but not multivariate, Cox regression analysis. CRC with OX40(high)/CD8(high) infiltration were characterized by significantly prolonged overall survival, as compared to tumors with OX40(low)/CD8(high), OX40(high)/CD8(low) or OX40(low)/CD8(low) infiltration in both uni- and multivariate analysis. In contrast, prognostic significance of OX40+ and FOXP3+ cell infiltration was not enhanced by a combined evaluation. Irrespective of TNM stage, CRC with OX40(high)/CD8(high) density infiltrates showed an overall survival similar to that of all stage I CRC included in the study.<br />Conclusions: OX40(high)/CD8(high) density tumor infiltration represents an independent, favorable, prognostic marker in CRC with an overall survival similar to stage I cancers.
- Subjects :
- Adult
Aged
Aged, 80 and over
Biomarkers, Tumor genetics
CD8 Antigens genetics
CD8-Positive T-Lymphocytes metabolism
Colorectal Neoplasms genetics
Colorectal Neoplasms immunology
Colorectal Neoplasms mortality
Female
Follow-Up Studies
Forkhead Transcription Factors genetics
Humans
Immunoenzyme Techniques
Lymphocytes, Tumor-Infiltrating metabolism
Male
Middle Aged
Neoplasm Grading
Neoplasm Staging
Prognosis
RNA, Messenger genetics
Real-Time Polymerase Chain Reaction
Receptors, OX40 genetics
Reverse Transcriptase Polymerase Chain Reaction
Survival Rate
Tissue Array Analysis
Biomarkers, Tumor metabolism
CD8 Antigens metabolism
CD8-Positive T-Lymphocytes immunology
Colorectal Neoplasms metabolism
Forkhead Transcription Factors metabolism
Lymphocytes, Tumor-Infiltrating immunology
Receptors, OX40 metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1949-2553
- Volume :
- 6
- Issue :
- 35
- Database :
- MEDLINE
- Journal :
- Oncotarget
- Publication Type :
- Academic Journal
- Accession number :
- 26439988
- Full Text :
- https://doi.org/10.18632/oncotarget.5940