Abstract

Inflammatory cells are involved in tumour initiation and progression. In parallel, the adaptive immune response plays a key role in fighting tumour growth and dissemination. The double-edged role of the immune system in solid tumours is well represented in colorectal cancer (CRC). The development and progression of CRC are affected by the interactions between the tumour and the host's response, occurring in a milieu named tumour microenvironment. The role of immune cells in human CRC is being unravelled and there is a strong interest in understanding their dynamics as to tumour promotion, immunosurveillance and immunoevasion. A better definition of immune infiltration would be important not only with respect to the ‘natural history’ of CRC, but in a clinically relevant perspective in the 21st century, with respect to its post-surgical management, including chemotherapy responsiveness. While it is becoming established that the amount of tumour-infiltrating lymphocytes influences the post-surgical progression of early-stage CRC, the relevance of this immune parameter as to chemotherapy responsiveness remains to be clarified. Despite recent experimental work supporting the notion that infiltrating immune cells may influence chemotherapy-mediated tumour cell death, tumour-infiltrating cells are not employed to identify patients who are more likely to benefit from adjuvant treatment. This review focuses on studies addressing the role of innate and adaptive immune cells along the occurrence and the progression of potentially curable CRC.

Highlights

  • This paper provides phenomenological and clinical evidence that the progression of colorectal cancer (CRC) across TNM stages parallels the need for cancer cells to undergo immune evasion (Fig. 1)

  • Translational and clinical studies to understand whether adaptive immune cells or other cellular players control the growth of CRC micro-metastasis and their interactions in the setting of chemotherapy are warranted

  • The evidence that CRC is a heterogeneous, multifactorial disease with different outcomes, prognosis and/or response to treatments in histologically equivalent tumours is suggestive of the complexity of cancer behaviour along its progression

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Summary

Introduction

The most relevant prognostic factor for CRC survival and recurrence is the presence of tumour cells in regional lymph nodes at histopathological examination, which identifies stage III patients [3]. Besides chronic inflammation, which is thought to be critically involved in tumour occurrence, experimental and clinical evidence has revealed a protective role for immune cells along cancer progression.

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