DOI QR코드

DOI QR Code

A Case of Canine Colorectal Carcinoma In Situ with Regulatory T Cell Infiltration

  • Yunhee Joung (Laboratory of Veterinary Internal Medicine, College of Veterinary Medicine, Jeju National University) ;
  • Jiwoong Yoon (College of Veterinary Medicine, Jeju National University) ;
  • Dong Ju Lee (College of Veterinary Medicine, Jeju National University) ;
  • Woo-Jin Song (Laboratory of Veterinary Internal Medicine, College of Veterinary Medicine, Jeju National University) ;
  • Jongtae Cheong (Department of Veterinary Medicine, College of Veterinary Medicine and Veterinary Medical Research Institute, Jeju National University) ;
  • Hyunjung Park (Department of Veterinary Medicine, College of Veterinary Medicine and Veterinary Medical Research Institute, Jeju National University) ;
  • Young-min Yun (Department of Veterinary Internal Medicine, Wildlife Rescue Center, College of Veterinary Medicine, Jeju National University) ;
  • Gee Euhn Choi (Research Institute of Veterinary Medicine, College of Veterinary Medicine, Jeju National University) ;
  • Myung-Chul Kim (Research Institute of Veterinary Medicine, College of Veterinary Medicine, Jeju National University)
  • Received : 2024.05.27
  • Accepted : 2024.07.16
  • Published : 2024.08.31

Abstract

An adult castrated male dog was presented with persistent hematochezia. Digital rectal examination and endoscopy found multiple colorectal masses. Complete blood count and serum biochemical results were within the reference interval. Fine needle aspirate of the masses indicated a diagnosis of inflamed polyps with a primary differential of malignancy. Histopathologic examination using endoscopy-guided incisional biopsy of the masses revealed an inflamed neoplasm with ossification. A colectomy was performed to remove the tumor. Subsequent histopathologic examination of the surgically resected masses resulted in a diagnosis of colorectal carcinoma in situ (CiS) with immune infiltrates, which were subject to immunohistochemical and flow cytometric immunophenotyping. The immunohistochemistry confirmed intraepithelial CD3+ T cells within CiS. The flow cytometric analysis indicated tumor-infiltrating CD4+ T, CD8+ T, and CD11b+ myeloid subsets. The flow cytometric analysis of circulating and tumor-infiltrating leukocytes demonstrated a preferential expansion of CD25+FOXP3+ regulatory T cells within CiS. To the author's knowledge, this is the first report to show clinical evidence emphasizing the immunogenicity and immune-suppressive environment of canine colorectal CiS. Our case will be valuable in providing a rationale for basic research that dissects the immune environment for canine colorectal cancers for the future development of cancer immunotherapy.

Keywords

Acknowledgement

The authors express sincere appreciation to all the pathologists from IDEXX Laboratories involved with the pathology and immunohistochemistry reports used in this study. This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (MOE) (#RS-2023-00241779).

References

  1. Biller BJ, Elmslie RE, Burnett RC, Avery AC, Dow SW. Use of FoxP3 expression to identify regulatory T cells in healthy dogs and dogs with cancer. Vet Immunol Immunopathol 2007; 116: 69-78.  https://doi.org/10.1016/j.vetimm.2006.12.002
  2. Cantatore M, Jimeno Sandoval JC, Das S, Sesana A, Charlesworth T, Ryan T, et al. Submucosal resection via a transanal approach for treatment of epithelial rectal tumors - a multicenter study. Vet Surg 2022; 51: 397-408.  https://doi.org/10.1111/vsu.13766
  3. Danova NA, Robles-Emanuelli JC, Bjorling DE. Surgical excision of primary canine rectal tumors by an anal approach in twenty-three dogs. Vet Surg 2006; 35: 337-340.  https://doi.org/10.1111/j.1532-950X.2006.00154.x
  4. Hayden DW, Nielsen SW. Canine alimentary neoplasia. Zentralbl Veterinarmed A 1973; 20: 1-22.  https://doi.org/10.1111/j.1439-0442.1973.tb00859.x
  5. Herstad KM, Gunnes G, Rortveit R, Kolbjornsen O, Tran L, Skancke E. Immunohistochemical expression of β-catenin, Ki67, CD3 and CD18 in canine colorectal adenomas and adenocarcinomas. BMC Vet Res 2021; 17: 119. 
  6. Horiuchi Y, Tominaga M, Ichikawa M, Yamashita M, Jikumaru Y, Nariai Y, et al. Increase of regulatory T cells in the peripheral blood of dogs with metastatic tumors. Microbiol Immunol 2009; 53: 468-474.  https://doi.org/10.1111/j.1348-0421.2009.00144.x
  7. Igase M, Inanaga S, Nishibori S, Itamoto K, Sunahara H, Nemoto Y, et al. Proof-of-concept study of the caninized anti-canine programmed death 1 antibody in dogs with advanced non-oral malignant melanoma solid tumors. J Vet Sci 2024; 25: e15. 
  8. Igase M, Nemoto Y, Itamoto K, Tani K, Nakaichi M, Sakurai M, et al. A pilot clinical study of the therapeutic antibody against canine PD-1 for advanced spontaneous cancers in dogs. Sci Rep 2020; 10: 18311. 
  9. Kan L, Liu Y, McGuire TL, Berger DM, Awatramani RB, Dymecki SM, et al. Dysregulation of local stem/progenitor cells as a common cellular mechanism for heterotopic ossification. Stem Cells 2009; 27: 150-156.  https://doi.org/10.1634/stemcells.2008-0576
  10. Kim MC, Borcherding N, Ahmed KK, Voigt AP, Vishwakarma A, Kolb R, et al. CD177 modulates the function and homeostasis of tumor-infiltrating regulatory T cells. Nat Commun 2021; 12: 5764. 
  11. Kim MC, Go DM, Woo SH, Oh JS, Kim DY, Kim NY, et al. A case of visceral T cell lymphoma with prominent histiocyte infiltration in a dog. J Vet Clin 2023; 40: 387-392.  https://doi.org/10.17555/jvc.2023.40.5.387
  12. Li C, Jiang P, Wei S, Xu X, Wang J. Regulatory T cells in tumor microenvironment: new mechanisms, potential therapeutic strategies and future prospects. Mol Cancer 2020; 19: 116. 
  13. Lin Z, Chen Q, Zhou J, Zhang J, Zhang X, Zhang D, et al. Transcriptomic analysis reveals immune infiltration status and potential biomarkers of canine colorectal cancer. Vet Immunol Immunopathol 2023; 262: 110622. 
  14. Liu X, Xu J, Chen L. Colorectal carcinoma with osseous metaplasia. Oncotarget 2017; 8: 65407-65413.  https://doi.org/10.18632/oncotarget.18577
  15. Maeda S, Motegi T, Iio A, Kaji K, Goto-Koshino Y, Eto S, et al. Anti-CCR4 treatment depletes regulatory T cells and leads to clinical activity in a canine model of advanced prostate cancer. J Immunother Cancer 2022; 10: e003731. 
  16. Maeda S, Murakami K, Inoue A, Yonezawa T, Matsuki N. CCR4 blockade depletes regulatory T cells and prolongs survival in a canine model of bladder cancer. Cancer Immunol Res 2019; 7: 1175-1187.  https://doi.org/10.1158/2326-6066.CIR-18-0751
  17. Maekawa N, Konnai S, Nishimura M, Kagawa Y, Takagi S, Hosoya K, et al. PD-L1 immunohistochemistry for canine cancers and clinical benefit of anti-PD-L1 antibody in dogs with pulmonary metastatic oral malignant melanoma. NPJ Precis Oncol 2021; 5: 10. 
  18. Meric T, Issard J, Maufras T, Hugonnard M, Senecat O, Lecoindre A, et al. Recurrence and survival in dogs with excised colorectal polyps: a retrospective study of 58 cases. J Vet Intern Med 2023; 37: 2375-2384.  https://doi.org/10.1111/jvim.16876
  19. Meuten DJ. Tumors in domestic animals. 5th ed. Ames: John Wiley & Sons. 2020. 
  20. Meyers C, Lisiecki J, Miller S, Levin A, Fayad L, Ding C, et al. Heterotopic ossification: a comprehensive review. JBMR Plus 2019; 3: e10172. 
  21. Morello E, Martano M, Squassino C, Iussich S, Caccamo R, Sammartano F, et al. Transanal pull-through rectal amputation for treatment of colorectal carcinoma in 11 dogs. Vet Surg 2008; 37: 420-426.  https://doi.org/10.1111/j.1532-950X.2008.00404.x
  22. Nucci DJ, Liptak JM, Selmic LE, Culp WT, Durant AM, Worley D, et al. Complications and outcomes following rectal pull-through surgery in dogs with rectal masses: 74 cases (2000-2013). J Am Vet Med Assoc 2014; 245: 684-695.  https://doi.org/10.2460/javma.245.6.684
  23. O'Neill K, Guth A, Biller B, Elmslie R, Dow S. Changes in regulatory T cells in dogs with cancer and associations with tumor type. J Vet Intern Med 2009; 23: 875-881.  https://doi.org/10.1111/j.1939-1676.2009.0333.x
  24. Sakai K, Maeda S, Yamada Y, Chambers JK, Uchida K, Nakayama H, et al. Association of tumour-infiltrating regulatory T cells with adverse outcomes in dogs with malignant tumours. Vet Comp Oncol 2018; 16: 330-336.  https://doi.org/10.1111/vco.12383
  25. Smith AA, Frimberger AE, Moore AS. Retrospective study of survival time and prognostic factors for dogs with small intestinal adenocarcinoma treated by tumor excision with or without adjuvant chemotherapy. J Am Vet Med Assoc 2019; 254: 243-250.  https://doi.org/10.2460/javma.254.2.243
  26. Takeuchi H, Konnai S, Maekawa N, Takagi S, Ohta H, Sasaki N, et al. Canine transforming growth factor-β receptor 2-Ig: a potential candidate biologic for melanoma treatment that reverses transforming growth factor-β1 immunosuppression. Front Vet Sci 2021; 8: 656715. 
  27. Valerius KD, Powers BE, McPherron MA, Hutchison JM, Mann FA, Withrow SJ. Adenomatous polyps and carcinoma in situ of the canine colon and rectum: 34 cases (1982-1994). J Am Anim Hosp Assoc 1997; 33: 156-160.  https://doi.org/10.5326/15473317-33-2-156
  28. Willard MD. Alimentary neoplasia in geriatric dogs and cats. Vet Clin North Am Small Anim Pract 2012; 42: 693-706, vi.  https://doi.org/10.1016/j.cvsm.2012.04.006
  29. Wolf JC, Ginn PE, Homer B, Fox LE, Kurzman ID. Immunohistochemical detection of p53 tumor suppressor gene protein in canine epithelial colorectal tumors. Vet Pathol 1997; 34: 394-404. https://doi.org/10.1177/030098589703400503