Correlation of Tumor-associated Leukocytes with Prognosis of Colorectal Carcinoma based on Pathologic Stage
DOI:
https://doi.org/10.21141/PJP.2019.12Keywords:
colorectal adenocarcinoma, tumor-infiltrating lymphocytes, peritumoral leukocytes, prognosisAbstract
Objectives To perform a pilot study investigating the presence of correlation between the different mean tumor-associated leukocyte counts and the prognosis of colorectal cancer based on pathologic stage.
Methodology A cross-sectional study design, involving colorectal carcinoma cases in the Philippine General Hospital from 2015-2016. Proportional allocation stratified random sampling was done, with pathologic stage (AJCC 7th Edition) as the stratifying variable, collecting a total of 59 samples. Tissue sections from the samples were evaluated for the different tumor-associated lymphocyte counts. Correlation coefficients were computed to determine their correlation with pathologic stage as surrogate marker for prognosis.
Results Of the myriad populations counted within and around the tumor mass, total lymphocyte, cytotoxic T-cell (CD8+ T-cell), neutrophil, macrophage, and plasma cell populations have significant correlation with pathologic stage as surrogate marker for prognosis of colorectal carcinoma.
Conclusion The immune system appears to have a significant role in the natural history of colorectal carcinoma. The tumor-infiltrating lymphocytic population and especially the CD8+ T-cell subset, neutrophils, and macrophages are correlated with better prognosis. The same observation can be seen with the peritumoral CD8+ T-cells, neutrophils, macrophages, and plasma cells.
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2. Medzhitov R. Origin and physiological roles of inflammation. Nature. 2008;454(7203):428-35. https://pubmed.ncbi.nlm.nih.gov/18650913. https://doi.org/10.1038/nature07201.
3. Fridman WH, Pagès F, Sautès-Fridman C, Galon J. The immune contexture in human tumours: impact on clinical outcome. Nat Rev Cancer. 2012;12(4):298-306. https://pubmed.ncbi.nlm.nih.gov/22419253. https://doi.org/10.1038/nrc3245.
4. DeNardo DG, Andreu P, Coussens LM. Interactions between lymphocytes and myeloid cells regulate pro- versus anti-tumor immunity. Cancer Metastasis Rev. 2010;29(2):309-16. https://pubmed.ncbi.nlm.nih.gov/20405169. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2865635. https://doi.org/10.1007/s10555-010-9223-6.
5. Kovacsovics-Bankowski M, Chisholm L, Vercellini J, et al. Detailed characterization of tumor infiltrating lymphocytes in two distinct human solid malignancies show phenotypic similarities. J Immunother Cancer. 2014;2(1):38. https://pubmed.ncbi.nlm.nih.gov/25436113. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4247679. https://doi.org/10.1186/s40425-014-0038-9.
6. Reissfelder C, Stamova S, Gossmann C, et al. Tumor specific cytotoxic T lymphocyte activity determines colorectal cancer patient prognosis. J Clin Invest. 2015;125(2):739-51. https://pubmed.ncbi.nlm.nih.gov/25562322. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4319435. https://doi.org/10.1172/JCI74894.
7. Huh JW, Lee JH, Kim HR. Prognostic significance of tumor-infiltrating lymphocytes for patients
with colorectal cancer. Arch Surg. 2012;147(4):366-72. https://pubmed.ncbi.nlm.nih.gov/22508783. https://doi.org/10.1001/archsurg.2012.35.
8. Tougeron D, Fauquembergue E, Rouquette A, et al. Tumor-infiltrating lymphocytes in colorectal cancers with microsatellite instability are correlated with the number and spectrum of frameshift mutations. Mod Pathol. 2009;22(9):1186-95. https://pubmed.ncbi.nlm.nih.gov/19503063. https://doi.org/10.1038/modpathol.2009.80.
9. Smyrk TC, Watson P, Kaul K, Lynch HT. Tumor infiltrating lymphocytes are a marker for microsatellite instability in colorectal carcinoma. Cancer. 2001;91(12):2417-22. https://pubmed.ncbi.nlm.nih.gov/11413533.
10. Ropponen KM, Eskelinen MJ, Lipponen PK, Alhava E, Kosma V-M. Prognostic value of tumour infiltrating lymphocytes (TILs) in colorectal cancer. J Pathol 1997;182(3):318-24. https://pubmed.ncbi.nlm.nih.gov/9349235.
11. Mendelsohn J, Howley P, Israel M, Gray J, Thompson C. The Molecular Basis of Cancer, 4th ed. Elsevier; 2014.
12. Fridlender ZG, Sun J, Kim S, et al. Polarization of tumor-associated neutrophil phenotype by TGFbeta:"N1" versus "N2" TAN. Cancer Cell. 2009;16(3):183-94. https://pubmed.ncbi.nlm.nih.gov/19732719. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2754404. https://doi.org/10.1016/j.ccr.2009.06.017.
13. López-Lago MA, Posner S, Thodima VJ, Molina AM, Motzer RJ, Chaganti RS. Neutrophil chemokines secreted by tumor cells mount a lung antimetastatic response during renal cell carcinoma progression. Oncogene. 2013;32(14):1752-60. https://pubmed.ncbi.nlm.nih.gov/22665059. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3435490. https://doi.org/10.1038/onc.2012.201.
14. Granot Z, Henke E, Comen EA, King TA, Norton L, Benezra R. Tumor entrained neutrophils inhibit seeding in the premetastatic lung. Cancer Cell. 2011;20(3):300-14. https://pubmed.ncbi.nlm.nih.gov/21907922. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3172582. https://doi.org/10.1016/j.ccr.2011.08.012.
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