Advances in Clinical and Experimental Medicine

Title abbreviation: Adv Clin Exp Med
JCR Impact Factor (IF) – 2.1 (5-Year IF – 2.0)
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ISSN 1899–5276 (print)
ISSN 2451-2680 (online)
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Advances in Clinical and Experimental Medicine

2020, vol. 29, nr 6, June, p. 715–725

doi: 10.17219/acem/121922

Publication type: original article

Language: English

License: Creative Commons Attribution 3.0 Unported (CC BY 3.0)

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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

Hiroyasu Matsuoka1,A,B,C,D,E,F, Hirochika Matsubara1,D,E,F, Aya Sugimura1,C,F, Tsuyoshi Uchida1,C,F, Tamo Kunimitsu1,C,F, Tomofumi Ichihara1,C,F, Yuichiro Oonuki2,C,F, Yoshihiro Miyauchi2,C,F, Tetsuo Kondo3,A,C, Hiroyuki Nakajima1,A,C,F

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

Abstract

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.

Key words

adenocarcinoma, prognosis, T-lymphocytes, regulatory

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