Abstract 2735: Clinical significance of CD4+CD7−helper T-cells and tumoral CD7 expression in colorectal cancer
Authors: Blessin Niclas Christian , Yang Cheng , Lennartz Maximilian , Möller Katharina , Mandelkow Tim , Simon Ronald , Sauter Guido , Fraune Christoph , Höflmayer Doris , Minner Sarah , Burandt Eike , Weidemann Sören A , Luebke Andreas M 
Published: July 2021

Abstract
CD7 is a transmembrane costimulatory glycoprotein and a member of the immunoglobulin supergene family, which is present on all thymocytes, most mature peripheral blood T-cells, and on natural killer (NK) cells. Studies indicate that the number of CD7 negative (CD7−) T-cells increases with age and in diseases such as chronic inflammation and in T-cell malignancies. To better understand the clinical relevance of CD7 expression in colon cancers and their immune microenvironment, tissue microarrays containing 1719 colorectal cancers were analyzed for CD3, CD4, CD8 and CD7 by multiplex fluorescence immunohistochemistry. Image analysis was performed using a U-net deep learning algorithm for cell detection and the “R” software package for statistical analysis. The density of CD3+CD4+ T-cells ranged from 0 to 8483 cells/mm2 (mean 504±686 cells/mm2) and the density of CD3+CD8+ T-cells ranged from 0 to 1386 cells/mm2 (mean 86±129 cells/mm2) in colorectal cancer. A high density of both, CD3+CD4+ helper T-cells and of CD3+CD8+ cytotoxic T-cells were associated with favorable tumor parameters, such as low tumor stage (p≤0.0004 each), negative nodal stage (p&lt;0.0001 each) or absence of lymphatic vessel invasion (p≤0.0002 each) and high PD-L1 expression in immune cells (p&lt;0.0001 each). In addition, a high density of CD3+CD8+ cytotoxic T-cells was linked to microsatellite instability (p&lt;0.0001) and PD-L1 expression on tumor cells.The average fraction of T-cells lacking CD7 was 22% for CD3+CD4+ T-cells and 1% for CD3+CD8+ T-cells. A low fraction of CD3+CD4+CD7− T-cells was linked to low pT stage (p&lt;0.0001) and microsatellite instability (p=0,0118) and tumor cell PD-L1 expression (p=0.0319) while the fraction of CD3+CD8+CD7− T-cells was unrelated to clinico-pathological parameters. Unequivocal membranous CD7 expression in cancer cells was found in 14 (0.8%) of cases and was significantly linked to lymphatic vessel invasion (p=0.0057) and perineural invasion (p=0.0045).In conclusion, the significant association of the fraction of CD3+CD4+CD7− T helper -cells with favorable clinicopathological features may suggest a clinically relevant role of this cell type. The rare CD7 positive colorectal cancers may potentially benefit from anti-CD7 therapies that are currently considered for T-cell neoplasias.
Citation Format: Niclas Christian Blessin, Cheng Yang, Maximilian Lennartz, Katharina Möller, Tim Mandelkow, Ronald Simon, Guido Sauter, Christoph Fraune, Doris Höflmayer, Sarah Minner, Eike Burandt, Sören A Weidemann, Andreas M Luebke. Clinical significance of CD4+CD7−helper T-cells and tumoral CD7 expression in colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2735.