The clinical utility of the local inflammatory response in colorectal cancer

Eur J Cancer. 2014 Jan;50(2):309-19. doi: 10.1016/j.ejca.2013.09.008. Epub 2013 Oct 5.

Abstract

Background: The host immune response is important in the prevention of tumour progression in solid organ cancers. The aim was to evaluate the clinical utility of the local inflammatory response in patients with colorectal cancer.

Methods: Three hundred and sixty-five patients with primary operable colorectal cancer were included. The local inflammatory response was assessed using three different methods; (1) individual T-cell subtypes (CD3, CD8, CD45R0, FOXP3), (2) an immunohistochemistry-based immune score (Galon Immune Score) and (3) a histopathological assessment (Klintrup-Makinen grade). Relationships with tumour and host characteristics were established and the prognostic value of each method compared.

Results: A strong infiltration of tumour infiltrating lymphoctyes (TIL's) was associated with improved cancer-specific survival. When individual T-cell subtypes were considered, CD3-positive cells were the strongest predictor of survival at the invasive margin (CD3(+) IM) while CD8-positive cells were the strongest predictor in the cancer cell nests (CD8(+) CCN). Infiltration of T-cells was related to early tumour stage, expanding growth pattern and lower levels of venous invasion but was not influenced by host characteristics or degree of systemic inflammation. In summary, CD3(+) IM, CD8(+) CCN, The Galon Immune Score and the Klintrup-Makinen grade all exhibited similar survival relationships in both node-positive and node-negative colorectal cancer.

Conclusion: A coordinated adaptive immune response is an important factor in predicting outcome in patients with primary operable colorectal cancer. By comparing different methodologies we have provided a foundation on which to develop a standardised approach for assessing the local inflammatory response in these patients.

Keywords: Colorectal cancer; Host response; Inflammation; Lymphocytes; Malignancy; Outcome; Prognosis; Survival.

MeSH terms

  • Aged
  • CD3 Complex / immunology
  • CD3 Complex / metabolism
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism
  • Colorectal Neoplasms / immunology*
  • Colorectal Neoplasms / pathology
  • Female
  • Forkhead Transcription Factors / immunology
  • Forkhead Transcription Factors / metabolism
  • Humans
  • Immunohistochemistry
  • Inflammation / immunology*
  • Inflammation / pathology
  • Kaplan-Meier Estimate
  • Leukocyte Common Antigens / immunology
  • Leukocyte Common Antigens / metabolism
  • Lymphocytes, Tumor-Infiltrating / immunology*
  • Lymphocytes, Tumor-Infiltrating / metabolism
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Prognosis
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / metabolism

Substances

  • CD3 Complex
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • Leukocyte Common Antigens