Characterization of colorectal cancer by hierarchical clustering analyses of five immune cell markers
Sunao Ito
Department of Gastroenterological Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
Search for more papers by this authorAkira Koshino
Division of Gastroenterology, Department of Internal Medicine, Aichi Medical University School of Medicine, Nagakute, Japan
Search for more papers by this authorMasayuki Komura
Department of Experimental Pathology and Tumor Biology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
Search for more papers by this authorShunsuke Kato
Division of Gastroenterology, Department of Internal Medicine, Aichi Medical University School of Medicine, Nagakute, Japan
Search for more papers by this authorTakahiro Otani
Department of Public Health, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
Search for more papers by this authorChengbo Wang
Department of Experimental Pathology and Tumor Biology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
Search for more papers by this authorAkane Ueki
Department of Experimental Pathology and Tumor Biology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
Search for more papers by this authorHiroki Takahashi
Department of Gastroenterological Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
Search for more papers by this authorMasahide Ebi
Division of Gastroenterology, Department of Internal Medicine, Aichi Medical University School of Medicine, Nagakute, Japan
Search for more papers by this authorNaotaka Ogasawara
Division of Gastroenterology, Department of Internal Medicine, Aichi Medical University School of Medicine, Nagakute, Japan
Search for more papers by this authorToyonori Tsuzuki
Surgical Pathology, Aichi Medical University School of Medicine, Nagakute, Japan
Search for more papers by this authorKenji Kasai
Department of Pathology, Aichi Medical University School of Medicine, Nagakute, Japan
Search for more papers by this authorKunio Kasugai
Division of Gastroenterology, Department of Internal Medicine, Aichi Medical University School of Medicine, Nagakute, Japan
Search for more papers by this authorShuji Takiguchi
Department of Gastroenterological Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
Search for more papers by this authorSatoru Takahashi
Department of Experimental Pathology and Tumor Biology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
Search for more papers by this authorCorresponding Author
Shingo Inaguma
Department of Experimental Pathology and Tumor Biology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
Department of Pathology, Aichi Medical University School of Medicine, Nagakute, Japan
Department of Pathology, Nagoya City University East Medical Center, Nagoya, Japan
Correspondence Shingo Inaguma, Department of Pathology, Nagoya City University East Medical Center; Department of Experimental Pathology and Tumor Biology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan.
Email: [email protected]
Search for more papers by this authorSunao Ito
Department of Gastroenterological Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
Search for more papers by this authorAkira Koshino
Division of Gastroenterology, Department of Internal Medicine, Aichi Medical University School of Medicine, Nagakute, Japan
Search for more papers by this authorMasayuki Komura
Department of Experimental Pathology and Tumor Biology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
Search for more papers by this authorShunsuke Kato
Division of Gastroenterology, Department of Internal Medicine, Aichi Medical University School of Medicine, Nagakute, Japan
Search for more papers by this authorTakahiro Otani
Department of Public Health, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
Search for more papers by this authorChengbo Wang
Department of Experimental Pathology and Tumor Biology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
Search for more papers by this authorAkane Ueki
Department of Experimental Pathology and Tumor Biology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
Search for more papers by this authorHiroki Takahashi
Department of Gastroenterological Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
Search for more papers by this authorMasahide Ebi
Division of Gastroenterology, Department of Internal Medicine, Aichi Medical University School of Medicine, Nagakute, Japan
Search for more papers by this authorNaotaka Ogasawara
Division of Gastroenterology, Department of Internal Medicine, Aichi Medical University School of Medicine, Nagakute, Japan
Search for more papers by this authorToyonori Tsuzuki
Surgical Pathology, Aichi Medical University School of Medicine, Nagakute, Japan
Search for more papers by this authorKenji Kasai
Department of Pathology, Aichi Medical University School of Medicine, Nagakute, Japan
Search for more papers by this authorKunio Kasugai
Division of Gastroenterology, Department of Internal Medicine, Aichi Medical University School of Medicine, Nagakute, Japan
Search for more papers by this authorShuji Takiguchi
Department of Gastroenterological Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
Search for more papers by this authorSatoru Takahashi
Department of Experimental Pathology and Tumor Biology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
Search for more papers by this authorCorresponding Author
Shingo Inaguma
Department of Experimental Pathology and Tumor Biology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
Department of Pathology, Aichi Medical University School of Medicine, Nagakute, Japan
Department of Pathology, Nagoya City University East Medical Center, Nagoya, Japan
Correspondence Shingo Inaguma, Department of Pathology, Nagoya City University East Medical Center; Department of Experimental Pathology and Tumor Biology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan.
Email: [email protected]
Search for more papers by this authorAbstract
The present study analyzed the expression of five independent immunohistochemical markers, CD4, CD8, CD66b, CD68, and CD163, on immune cells within the colorectal cancer (CRC) tumor microenvironment (TME). Using hierarchical clustering, patients were successfully classified according to significant associations with clinicopathological features and/or survival. Patients with mismatch repair-proficient (pMMR) CRC were categorized into four groups with survival differences (p = 0.0084): CD4Low, CD4High, MΦHigh, and CD8Low. MΦHigh tumors showed significantly higher expression of CD47 (p < 0.0001), a phagocytosis checkpoint molecule. These tumors contained significantly greater numbers of PD-1+ (p < 0.0001), TIM-3+ (p < 0.0001), and SIRPA+ (p < 0.0001) immune cells. Notably, 10% of the patients with pMMR CRC expressed PD-L1 (CD274) on tumor cells with significantly worse survival (p = 0.00064). The Cox proportional hazards model identified MΦ High (hazard ratio [HR] = 2.02, 95%, p = 0.032), CD8Low (HR = 2.45, p = 0.011), and tumor PD-L1 expression (HR = 2.74, p = 0.0061) as potential risk factors. PD-L1–PD-1 and/or CD47–SIRPA axes targeting immune checkpoint therapies might be considered for patients with pMMR CRC according to their tumor cells and tumor immune microenvironment characteristics.
CONFLICT OF INTEREST STATEMENT
The authors have disclosed that they have no relationships with, or financial interest in, any commercial companies pertaining to this article. Toyonori Tsuzuki and Satoru Takahashi are an Editorial Board member of Pathology International and a co-author of this article. To minimize bias, they were excluded from all editorial decision-making related to the acceptance of this article for publication.
Supporting Information
| Filename | Description |
|---|---|
| pin13391-sup-0001-CRC_immune_cells_Supplementary_TableS1.docx35.7 KB | Supporting information. |
| pin13391-sup-0002-CRC_immune_cells_Supplementary_TableS2.docx30.9 KB | Supporting information. |
| pin13391-sup-0003-CRC_immune_cells_Supplementary_TableS3.docx22.3 KB | Supporting information. |
| pin13391-sup-0004-CRC_immune_cells_Supplementary_TableS4.docx22.9 KB | Supporting information. |
| pin13391-sup-0005-4.TIF456 KB | Supporting information. |
| pin13391-sup-0006-5.TIF143.1 KB | Supporting information. |
| pin13391-sup-0007-supmat.docx16.1 KB | Supporting information. |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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