Tumour-Infiltrating Lymphocytes in Colorectal Adenocarcinoma

  • Nursakti Hamzah Department of Pathology Anatomy, Faculty of Medicine, Hasanuddin University, Makassar, Indonesia
  • Syarifuddin Wahid Department of Pathology Anatomy, Faculty of Medicine, Hasanuddin University, Makassar, Indonesia
  • Ni Ketut Sungowati Department of Pathology Anatomy, Faculty of Medicine, Hasanuddin University, Makassar, Indonesia
  • Muhammad Husni Cangara Department of Pathology Anatomy, Faculty of Medicine, Hasanuddin University, Makassar, Indonesia
  • Andi Alfian Zainuddin Department of Pathology Anatomy, Faculty of Medicine, Hasanuddin University, Makassar, Indonesia
  • Upik Anderiani Miskad Department of Public Health, Faculty of Medicine, Hasanuddin University, Makassar, Indonesia
Keywords: TILs, colorectal cancer, adenocarcinoma, histological grading.


Several studies have indicated that lymphocytes found in tumour area, known as TILs (tumour-infiltrating lymphocytes), can provide prognostic information in colorectal cancer (CRC). The purpose of this study was to evaluate degree of stromal TILs  according to histological grading of CRC. This study used  a cross sectional design method by taking random samples of data and formalin-fixed paraffin-embedded of colorectal adenocarcinoma patients treated in Dr. Wahidin Sudirohusodo Hospital and Hasanuddin University Hospital in Makassar during the period of 2014-2016. The histological grading of each sample was reviewed and  TILs were assessed according to recommendation of the International TILs Working Group, 2014 on hematoxylin-eosin (H-E)-stained sections. Based on histological grading it was found that from 98 samples, 23 samples (23.5%) were well-differentiated, 66 samples (67.3%) were moderately differentiated, and 6 samples were (9.2%) poorly differentiated. While based on degree of TILs found that low- and moderate-score were 38 (38.8%) and 42 (42.9%) samples respectively, and high-score were 18 (18.4%) samples. Data were analysed using the Chi-square test and a p value of 0.865 (p > 0.05) was obtained and therefore it was concluded that there was no significant difference of degree of TILs according to histological grading of colorectal adenocarcinoma in this study.


Ferlay, J., Soerjomataram, I., Dikshit, R., Eser, S., Mathers, C., Rebelo, M., … Bray, F. (2015). Cancer incidence and mortality worldwide : Sources , methods and major patterns in GLOBOCAN 2012, 386. https://doi.org/10.1002/ijc.29210

Arnold, M., Sierra, M. S., Laversanne, M., Soerjomataram, I., Jemal, A., & Bray, F. (2017). Global patterns and trends in colorectal cancer incidence and mortality. Gut, 66(4), 683–691. https://doi.org/10.1136/gutjnl-2015-310912

WHO. (2014). Indonesia, cancer country profiles, 22–23.

Jakubowska, K., Kisielewski, W., & Koda, L. K. (2017). Stromal and intraepithelial tumor ‑ infiltrating lymphocytes in colorectal carcinoma, 6421–6432. https://doi.org/10.3892/ol.2017.7013

Yao, W., He, J., Yang, Y., Wang, J., Qian, Y., Yang, T., & Ji, L. (2017). The Prognostic Value of Tumor- infiltrating Lymphocytes in Hepatocellular Carcinoma : a Systematic Review and Meta- analysis. Scientific Reports, (July), 1–11. https://doi.org/10.1038/s41598-017-08128-1

Gooden, M. J. M., Bock, G. H. De, Leffers, N., Daemen, T., & Nijman, H. W. (2011). The prognostic influence of tumour-infiltrating lymphocytes in cancer : a systematic review with meta-analysis. British Journal of Cancer, 105(1), 93–103. https://doi.org/10.1038/bjc.2011.189

Mei, Z., Liu, Y., Liu, C., Cui, A., Liang, Z., Wang, G., … Li, C. (2014). Tumour-infiltrating inflammation and prognosis in colorectal cancer : systematic review and meta-analysis, (February), 1595–1605. https://doi.org/10.1038/bjc.2014.46

Bupathi, M., & Wu, C. (2016). Biomarkers for immune therapy in colorectal cancer: mismatch-repair deficiency and others. Journal of Gastrointestinal Oncology, 7(5), 713–720. https://doi.org/10.21037/jgo.2016.07.03

.Abbas, A. K., Lichtman, A., & Pillai, S. (2017). Cellular and Molecular Immunology (9th ed.). Philadelphia: Elsevier Inc.

Rozek, L. S., Schmit, S. L., Greenson, J. K., Tomsho, L. P., Rennert, H. S., Rennert, G., & Gruber, S. B. (2016). Tumor-Infiltrating lymphocytes, Crohn’s-like lymphoid reaction, and survival from colorectal cancer. Journal of the National Cancer Institute, 108(8), 1–8. https://doi.org/10.1093/jnci/djw027

Hyuk, L. J. (2012). Prognostic Significance of Tumor-Infiltrating Lymphocytes for Patients With Colorectal Cancer. Archives of Surgery, 147(4), 366. https://doi.org/10.1001/archsurg.2012.35

Deschoolmeester, V., Baay, M., Lardon, F., Pauwels, P., & Peeters, M. (2011). Immune Cells in Colorectal Cancer : Prognostic Relevance and Role of MSI, 377–392. https://doi.org/10.1007/s12307-011-0068-5

Salgado, R., Denkert, C., Demaria, S., Sirtaine, N., Klauschen, F., Pruneri, G., … Loi, S. (2015). The evaluation of tumor-infiltrating lymphocytes (TILS) in breast cancer: Recommendations by an International TILS Working Group 2014. Annals of Oncology, 26(2), 259–271. https://doi.org/10.1093/annonc/mdu450

Stanley R. Hamilton, M. D., & Lauri A. Aaltonen, M.D., P. D. (2000). World Health Organization Classification of Tumours, Pathology and Genetics of Tumours of the Digestive System (Vol. 18). https://doi.org/10.1183/09031936.01.00275301

.Marzouk, O., & Schofield, J. (2011). Review of histopathological and molecular prognostic features in colorectal cancer. Cancers, 3(2), 2767–2810. https://doi.org/10.3390/cancers3022767

Iseki, Y., Shibutani, M., Maeda, K., & Nagahara, H. (2018). A new method for evaluating tumor- infiltrating lymphocytes ( TILs ) in colorectal cancer using hematoxylin and eosin ( H-E ) - stained tumor sections, 1–12.

Shi, S., Wang, L., Wang, G., Guo, Z., Wei, M., & Meng, Y. (2013). B7-H1 Expression Is Associated with Poor Prognosis in Colorectal Carcinoma and Regulates the Proliferation and Invasion of HCT116 Colorectal Cancer Cells, 8(10), 1–11. https://doi.org/10.1371/journal.pone.0076012

Amersi, F., Agustin, M., & Ko, C. Y. (2005). Colorectal Cancer : Epidemiology , Risk Factors , and Health Services, 18(3), 133–140.

Dintinjana, R. D., Redzović, A., & Dintinjana, M. (2014). Molecular Pathways of Colorectal Carcinogenesis are Promising Mistery ?, 1–5. https://doi.org/10.4172/2157-2518.S10-003

Valentini, A. M., Pinto, F. Di, Cariola, F., Guerra, V., Caruso, M. L., & Pirrelli, M. (2018). PD-L1 expression in colorectal cancer defines three subsets of tumor immune microenvironments, 9(9), 8584–8596.

Rosenbaum, M. W., Bledsoe, J. R., Morales-Oyarvide, V., Huynh, T. G., & Mino-Kenudson, M. (2016). PD-L1 expression in colorectal cancer is associated with microsatellite instability, BRAF mutation, medullary morphology and cytotoxic tumor-infiltrating lymphocytes. Modern Pathology, 29(9), 1104–1112. https://doi.org/10.1038/modpathol.2016.95

Huszno, J., N., E. Z., Lange, D., K., Z., & Nowara, E. (2017). The association of tumor lymphocyte infiltration with clinicopathological factors and survival in breast cancer, 68(1), 26–32.

Dong, Y., Sun, Q., & Zhang, X. (2017). PD-1 and its ligands are important immune checkpoints in cancer, 8(2), 2171–2186.

Passardi, A., Canale, M., Valgiusti, M., & Ulivi, P. (2017). Immune checkpoints as a target for colorectal cancer treatment. International Journal of Molecular Sciences, 18(6). https://doi.org/10.3390/ijms18061324

Guo, L., Lin, Y., & Kwok, H. F. (2017). The function and regulation of PD-L1 in immunotherapy. ADMET and DMPK, 5(3), 159. https://doi.org/10.5599/admet.5.3.442

Karwacz, K., Arce, F., Bricogne, C., Kochan, G., & Escors, D. (2012). PD-L1 co-stimulation, ligand-induced TCR down-modulation and anti-tumor immunotherapy, 1(1), 86–88. https://doi.org/10.1002/emmm.201100165.www.landesbioscience.com

Mo, Z., Liu, J., Zhang, Q., Chen, Z., Mei, J., Liu, L., … You, Z. (2016). Expression of PD ‑ 1 , PD ‑ L1 and PD ‑ L2 is associated with differentiation status and histological type of endometrial cancer, 944–950. https://doi.org/10.3892/ol.2016.4744

Kawahara, T., Ishiguro, Y., Ohtake, S., Kato, I., Ito, Y., Ito, H., … Nakaigawa, N. (2018). PD-1 and PD-L1 are more highly expressed in high-grade bladder cancer than in low- grade cases : PD-L1 might function as a mediator of stage progression in bladder cancer, 1–6.

Masugi, Y., Nishihara, R., Yang, J., Mima, K., Da Silva, A., Shi, Y., … Ogino, S. (2017). Tumour CD274 (PD-L1) expression and T cells in colorectal cancer. Gut, 66(8), 1463–1473. https://doi.org/10.1136/gutjnl-2016-311421

Nishikawa, H., & Sakaguchi, S. (2010). Regulatory T cells in tumor immunity, 767, 759–767. https://doi.org/10.1002/ijc.2542