SLC1A5, unrelated to prognosis, was associated with CD8+ T-cell exclusion in the tumor microenvironment of squamous cell carcinoma

Shutao Zheng; Tao Liu; Lu Li; Qing Liu; Conggai Huang; Yan Liang; Yiyi Tan; Li Zhang; Xiaomei Lu

doi:10.1016/j.heliyon.2023.e14571

SLC1A5, unrelated to prognosis, was associated with CD8⁺ T-cell exclusion in the tumor microenvironment of squamous cell carcinoma

Heliyon. 2023 Mar 15;9(3):e14571. doi: 10.1016/j.heliyon.2023.e14571. eCollection 2023 Mar.

Authors

Shutao Zheng^{1

2}, Tao Liu³, Lu Li³, Qing Liu^{1

2}, Conggai Huang^{1

4}, Yan Liang⁵, Yiyi Tan², Li Zhang^{1

6}, Xiaomei Lu^{1

2}

Affiliations

¹ State Key Laboratory of Pathogenesis, Prevention, Treatment of Central Asian High Incidence Diseases, Xinjiang Uygur Autonomous Region, Urumqi, PR China.
² Clinical Medical Research Institute, First Affiliated Hospital of Xinjiang Medical University, Xinjiang Uygur Autonomous Region, Urumqi, PR China.
³ Department of Clinical Laboratory, First Affiliated Hospital of Xinjiang Medical University, Xinjiang Uygur Autonomous Region, Urumqi, PR China.
⁴ Department of Pathology, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, China.
⁵ Department of Pathology, Basic Medicine College, Xinjiang Medical University, Urumqi, 830017, China.
⁶ VIP Medicine, First Affiliated Hospital of Xinjiang Medical University, Xinjiang Uygur Autonomous Region, Urumqi, PR China.

Abstract

SLC1A5, short for solute carrier family 1 member 5, is a neutral amino acid transporter whose expression has been reported to be upregulated in various cancers, including esophageal squamous cell carcinoma (ESCC). Despite this, little has been described regarding the immunological involvement of SLC1A5 expression in the tumor microenvironment of ESCC. Given this, we adopted in silico analyses together with a wet lab strategy to investigate the prognostic and clinicopathological meaning of SLC1A5 expression in ESCC. In silico analyses of SLC1A5 expression data available from The Cancer Genome Atlas (TCGA) database revealed that SLC1A5 expression was unrelated to the prognosis of ESCC, which holds true when extended to other types of squamous cell carcinoma (SCC), including head and neck squamous cell carcinoma (HNSC) and lung squamous cell carcinoma (LUSC). Further analyses revealed that SLC1A5 expression correlated markedly with the infiltration density of effector CD8⁺ T cells in ESCC, and the same was true for HNSC and LUSC when extrapolated. As experimental confirmation, multiplexed immunofluorescent staining was undertaken to verify the correlation between SLC1A5 expression and infiltration of CD8⁺ T cells in a tissue microarray prepared from ESCC and matched normal control tissues. Our data confirmed that SLC1A5 expression was not associated with prognosis but was associated with the exclusion of CD8⁺ T cells. Taken together, all the data we curated strongly support the notion that SLC1A5 expression is associated with CD8⁺ T-cell exclusion in the tumor microenvironment of SCC.

Keywords: CD8+ T; Exclusion; Prognosis; SLC1A5; Squamous cell carcinoma (SCC).