STUDY OF TUMOR MICROENVIRONMENT AND HOST RESPONSE IN COLORECTAL CANCER: IMMUNOHISTOCHEMICAL AND CLINICOPATHOLOGICAL APPROACH

Authors

  • NORIA OTHMAN RAFFALLA Department of Pathology, Faculty of Medicine, University of Omar Al-Mukhtar, Al Bayda, Libya.
  • SUZAN MOHAMED FAROUK HELAL Department of Pathology, Faculty of Medicine, University of Alexandria, Alexandria Governorate, Egypt.
  • AMANY ABD EL-BARY ABD EL-LATIF Department of Pathology, Faculty of Medicine, University of Alexandria, Alexandria Governorate, Egypt.
  • RASHA OMAR ELSAKA Department of Clinical Oncology and Nuclear Medicine, Faculty of Medicine, University of Alexandria, Alexandria Governorate, Egypt.

DOI:

https://doi.org/10.22159/ajpcr.2020.v13i1.35940

Keywords:

Colorectal cancer, Lymphocyte subsets, Tumor-associated macrophage, Tertiary lymphoid structure, Survival

Abstract

Objective: This study aimed to evaluate the immunohistochemical expression of forkhead boxP3 (Foxp3), CD8, CD68, and CD21 in stroma between tumor cells of colorectal cancer (CRC) patients and examines the relationship between these variables and clinicopathological parameter and patients’ prognosis.

Methods: In this work, 50 cases of colorectal carcinomas were included and immunohistochemical evaluation of Foxp3, CD8, CD68, and CD21 in tumor tissue samples.

Results: Tumor-infiltrating lymphocytes (TILs) including cytotoxic T cells and regulatory T cells as well as tumor-associated macrophages and follicular dendritic cells (FDCs) were studied in the stroma of the tumor using immunostaining technique for CD8, Foxp3, CD68, and CD21, respectively. Cases were followed up. CD8-positive cytotoxic T cells, Foxp3-positive regulatory T cells, and CD21 positive-FDCs were significantly more pronounced in early tumors and those with longer overall survival. On the other hand, CD68 positive macrophages were more encountered in late stage and metastatic tumors as well as tumors with shorter overall survival, but these results not reached the level of significance.

Conclusion: We concluded that (TILs) and FDCs are conferring better prognosis in CRCs, they may act synergistically in stimulating a protective immune response in the tumor microenvironment that hinders tumor progression, while the role of tumor-associated macrophages in CRCs is still controversial and needs further studies.

Downloads

Download data is not yet available.

References

Aithal RR, Shetty RS, Binu VS, Mallya SD. Colorectal cancer and its risk factors among patients attending a tertiary care hospital in Southern Karnataka, India. Asian J Pharm Clin Res 2017;10:109-12.

Bano N, Najam R, Mirza T, Hassan S. Review of colorectal carcinoma and specific disease features in the population of Pakistan. Asian J Pharm Clin Res 2013;6 Suppl 1:13-7.

Khalifa SE, Khairy RA, Bassam AM. Expression of cathepsin D and BCL-2 in colorectal carcinoma, and their correlation with proliferation indices. Egypt J Pathol 2016;36:276-81.

Marley AR, Nan H. Epidemiology of colorectal cancer. Int J Mol Epidemiol Genet 2016;7:105-14.

Gandomani HS, Yousefi SM, Aghajani M, Mohammadian- Hafshejani AM, Tarazoj AA, Pouyesh V, et al. Colorectal cancer in the world: Incidence, mortality and risk factors. Biomed Res Ther 2017;4:1656-75.

Peddareddigari VG, Wang D, Dubois RN. The tumor microenvironment in colorectal carcinogenesis. Cancer Microenviron 2010;3:149-66.

Bhome R, Bullock MD, Al Saihati HA, Goh RW, Primrose JN, Sayan AE, et al. A top-down view of the tumor microenvironment: Structure, cells and signaling. Front Cell Dev Biol 2015;3:33.

Coppola D, Nebozhyn M, Khalil F, Dai H, Yeatman T, Loboda A, et al. Unique ectopic lymph node-like structures present in human primary colorectal carcinoma are identified by immune gene array profiling. Am J Pathol 2011;179:37-45.

Posch F, Silina K, Leibl S, Mündlein A, Moch H, Siebenhüner A, et al. Maturation of tertiary lymphoid structures and recurrence of stage II and III colorectal cancer. Oncoimmunology 2018;7:e1378844.

Trajkovski G, Ognjenovic L, Karadzov Z, Jota G, Hadzi-Manchev D, Kostovski O, et al. Tertiary lymphoid structures in colorectal cancers and their prognostic value. Open Access Maced J Med Sci 2018;6:1824-8.

Marks KM, West NP, Morris E, Quirke P. Clinicopathological, genomic and immunological factors in colorectal cancer prognosis. Br J Surg 2018;105:e99-109.

De Divitiis C, Nasti G, Montano M, Fisichella R, Iaffaioli RV, Berretta M. Prognostic and predictive response factors in colorectal cancer patients: Between hope and reality. World J Gastroenterol 2014;20:15049-59.

Svennevig JL, Lunde OC, Holter J, Bjørgsvik D. Lymphoid infiltration and prognosis in colorectal carcinoma. Br J Cancer 1984;49:375-7.

Rosai J. Special techniques in surgical pathology. In: Rosai J, Ackerman LV, editors. Rosai and Ackerman’s Surgical Pathology. 10th ed. Edinburgh: Mosby Elsevier; 2011. p. 37-95.

Jakovic LR, Mihaljevic BS, Perunicic Jovanovic MD, Bogdanovic AD, Andjelic BM, Bumbasirevic VZ. The prognostic relevance of tumor associated macrophages in advanced stage classical hodgkin lymphoma. Leuk Lymphoma 2011;52:1913-9.

Takenaka M, Seki N, Toh U, Hattori S, Kawahara A, Yamaguchi T, et al. Foxp3 expression in tumor cells and tumor-infiltrating lymphocytes is associated with breast cancer prognosis. Mol Clin Oncol 2013;1:625-32.

Chen Z, Chen X, Zhou E, Chen G, Qian K, Wu X, et al. Intratumoral CD8⁺ cytotoxic lymphocyte is a favorable prognostic marker in node-negative breast cancer. PLoS One 2014;9:e95475.

Sun X, Feng Z, Wang Y, Qu Y, Gai Y. Expression of Foxp3 and its prognostic significance in colorectal cancer. Int J Immunopathol Pharmacol 2017;30:201-6.

Ling A, Edin S, Wikberg ML, Öberg Å, Palmqvist R. The intratumoural subsite and relation of CD8(+) and Foxp3(+) T lymphocytes in colorectal cancer provide important prognostic clues. Br J Cancer 2014;110:2551-9.

Ladoire S, Martin F, Ghiringhelli F. Prognostic role of Foxp3+ regulatory T cells infiltrating human carcinomas: The paradox of colorectal cancer. Cancer Immunol Immunother 2011;60:909-18.

Grimmig T, Kim M, Germer CT, Gasser M, Waaga-Gasser AM. The role of Foxp3 in disease progression in colorectal cancer patients. Oncoimmunology 2013;2:e24521.

Michel S, Benner A, Tariverdian M, Wentzensen N, Hoefler P, Pommerencke T, et al. High density of Foxp3-positive T cells infiltrating colorectal cancers with microsatellite instability. Br J Cancer 2008;99:1867-73.

Kim M, Grimmig T, Grimm M, Lazariotou M, Meier E, Rosenwald A, et al. Expression of Foxp3 in colorectal cancer but not in treg cells correlates with disease progression in patients with colorectal cancer. PLoS One 2013;8:e53630.

Zhong X, Chen B, Yang Z. The role of tumor-associated macrophages in colorectal carcinoma progression. Cell Physiol Biochem 2018;45:356-65.

Hao NB, Lü MH, Fan YH, Cao YL, Zhang ZR, Yang SM. Macrophages in tumor microenvironments and the progression of tumors. Clin Dev Immunol 2012;2012:948098.

Murray PJ, Wynn TA. Protective and pathogenic functions of macrophage subsets. Nat Rev Immunol 2011;11:723-37.

Ruffell B, Affara NI, Coussens LM. Differential macrophage programming in the tumor microenvironment. Trends Immunol 2012;33:119-26.

Qian BZ, Pollard JW. Macrophage diversity enhances tumor progression and metastasis. Cell 2010;141:39-51.

Yahaya MA, Lila MA, Ismail S, Zainol M, Afizan NA. Tumour-associated macrophages (tams) in colon cancer and how to reeducate them. J Immunol Res 2019;2019:2368249.

Koelzer VH, Canonica K, Dawson H, Sokol L, Karamitopoulou- Diamantis E, Lugli A, et al. Phenotyping of tumor-associated macrophages in colorectal cancer: Impact on single cell invasion (tumor budding) and clinicopathological outcome. Oncoimmunology 2016;5:e1106677.

Waniczek D, Lorenc Z, Śnietura M, Wesecki M, Kopec A, Muc- Wierzgoń M. Tumor-associated macrophages and regulatory T cells infiltration and the clinical outcome in colorectal cancer. Arch Immunol Ther Exp (Warsz) 2017;65:445-54.

Cui YL, Li HK, Zhou HY, Zhang T, Li Q. Correlations of tumor-associated macrophage subtypes with liver metastases of colorectal cancer. Asian Pac J Cancer Prev 2013;14:1003-7.

Forssell J, Oberg A, Henriksson ML, Stenling R, Jung A, Palmqvist R. High macrophage infiltration along the tumor front correlates with improved survival in colon cancer. Clin Cancer Res 2007;13:1472-9.

Li S, Xu F, Zhang J, Wang L, Zheng Y, Wu X, et al. Tumor-associated macrophages remodeling EMT and predicting survival in colorectal carcinoma. Oncoimmunology 2018;7:e1380765.

Chaput N, Svrcek M, Aupérin A, Locher C, Drusch F, Malka D, et al. Tumour-infiltrating CD68+ and CD57+ cells predict patient outcome in stage II-III colorectal cancer. Br J Cancer 2013;109:1013-22.

Deschoolmeester V, Baay M, Van Marck E, Weyler J, Vermeulen P, Lardon F, et al. Tumor infiltrating lymphocytes: An intriguing player in the survival of colorectal cancer patients. BMC Immunol 2010;11:19.

Sideras K, Galjart B, Vasaturo A, Pedroza-Gonzalez A, Biermann K, Mancham S, et al. Prognostic value of intra-tumoral CD8+/Foxp3+ lymphocyte ratio in patients with resected colorectal cancer liver metastasis. J Surg Oncol 2018;118:68-76.

Shibutani M, Maeda K, Nagahara H, Fukuoka T, Matsutani S, Kashiwagi S, et al. A comparison of the local immune status between the primary and metastatic tumor in colorectal cancer: A retrospective study. BMC Cancer 2018;18:371.

Published

07-01-2020

How to Cite

NORIA OTHMAN RAFFALLA, SUZAN MOHAMED FAROUK HELAL, AMANY ABD EL-BARY ABD EL-LATIF, and RASHA OMAR ELSAKA. “STUDY OF TUMOR MICROENVIRONMENT AND HOST RESPONSE IN COLORECTAL CANCER: IMMUNOHISTOCHEMICAL AND CLINICOPATHOLOGICAL APPROACH”. Asian Journal of Pharmaceutical and Clinical Research, vol. 13, no. 1, Jan. 2020, pp. 32-37, doi:10.22159/ajpcr.2020.v13i1.35940.

Issue

Section

Original Article(s)