Advances in Clinical and Experimental Medicine
2020, vol. 29, nr 6, June, p. 715–725
Publication type: original article
Detecting tumor-infiltrating Forkhead box P3-positive T cells in the prognosis of lung adenocarcinoma: Possible role of clustering tumor interleukin-12 subunit alpha and transforming growth factor beta 1 expression
1 Department of Surgery, Faculty of Medicine, University of Yamanashi, Chuo, Japan
2 Department of Thoracic Surgery, National Hospital Organization Disaster Medical Center, Tachikawa, Tokyo, Japan
3 Department of Pathology, Faculty of Medicine, University of Yamanashi, Chuo, Japan
Background. While regulatory T cells (Tregs) are a poor prognostic factor for lung cancer, they may be detected as Forkhead box P3+ (FOXP3+) and cluster of differentiation (-CD) 4+ T cells by classifying FOXP3+CD4+ T cells into different subpopulations of CD4 cells.
Objectives. To classify clusters of tumor-infiltrating Tregs in lung adenocarcinoma based on the mRNA expression levels of interleukin-12 subunit alpha (IL12A) and transforming growth factor beta 1 (TGFB1) in tumor specimens.
Material and Methods. Seventy-nine patients with lung adenocarcinoma were evaluated in this study. Clinical data were obtained from the patients’ medical records, while tumor tissue samples were preserved as formalin-fixed paraffin-embedded (FFPE) tissue specimens. Immunohistochemical staining for CD4, CD8 and FOXP3 was performed and stained cell counts were obtained under 5 high-power fields. cDNA was synthesized from total RNA extracted from FFPE tissue specimens and amplified with Taqman probes for FOXP3, IL12A, TGFB1, and the glyceraldehyde-3-phosphate dehydrogenase gene.
Results. Two clusters were identified: IL12AlowTGFB1low (Cluster 1: n = 44) and IL12AhighTGFB1high (Cluster 2: n = 39). Although no significant difference in the FOXP3+ cell/CD4+ cell ratio was observed between the 2 clusters (p = 0.921), the high FOXP3+/CD4+ cell ratio group showed a significantly poorer relapse-free survival rate than the low FOXP3+/CD4+ cell ratio group in Cluster 1 (p = 0.031).
Conclusion. Although the results revealed no direct association between Tregs and prognosis according to each subtype, these results suggest that if a lung cancer specimen contains low levels of IL12A and TGFB1, the FOXP3+/CD4+ cell ratio is useful for predicting the prognosis of lung cancer.
adenocarcinoma, prognosis, T-lymphocytes, regulatory
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