Immune response at tumour site predicts cancer progression in colorectal cancer patients

The immune reaction at tumour site determines cancer evolution and clinical outcome in patients with colorectal cancer, regardless of the local extent and spread of the tumour, according to the findings of Jérôme Galon, INSERM Research Director, Paris, and co-workers. The analysis of immunological parameters should therefore be integrated into the process of staging and clinical decision finding, says Galon at the 2nd European Congress of Immunology ECI 2009.

Colorectal cancer is one of the most common malignancies, with an estimated annual incidence of one million cases worldwide. The prognosis is severe, with a 5-year-survival of 55 %. Surgical resection is effective for localized disease. An additional  post-surgical course of chemotherapy is reserved for patients with lymph node or distant metastases. But also a significant proportion of patients with local disease (Stage I/II patients) develops recurrence and dies from the disease. "There is clearly a need to identify novel predictive factors to identify patients with the potential for colon cancer progression", Galon stresses.

Actually, assessing patient survival and choosing the optimal therapy are based on the currently used classification. Staging includes tumour size, local spread and distant metastases. Galon und co-workers showed that a detailed analysis of local immune reaction would be a better predictor, especially in identifying high risk patients with minimal invasive tumours.

Galon analysed the infiltration of lymphocytes, the most important cells of immune response, into the tumour and peritumoural tissue in 415 patients with colorectal cancer. The scientist developed a comprehensive analysis of the nature, the functional orientation, the density and the organization of the immune cell populations within the tumour. He performed a large-scale analysis of in situ immune parameters as well as an original analysis of gene expression, which enables the identification of genes whose co-expression is correlated with cancer evolution. These data were confirmed in a blinded manner in two independent patient cohorts>

All statistical analyses reveal the strength of the in situ immune contexture on clinical outcome at all stages of the disease. High density of immune cells correlated with an equally favourable prognosis regardless of the cancer size and spread. Conversely, a weak immune response correlated with a very poor prognosis even in patients with minimal tumour invasion. „This has never been shown in any human tumour", says Galon. As a consequence this should lead to recast the currently used classification of colorectal cancers for predicting clinical outcome, and refine the patient groups that are at high-risk of tumour recurrence that may benefit from adjuvant theapy, including immunotherapy.

Recent data of 602 stage I-II patients with colorectal cancer from two independent cohorts emphasize the crucial role of two T cell populations: the cytotoxic (CD8) and the memory T cells. Memory T cells obviously control the early steps of the metastatic process. They may have a central role in the control of tumour spreading along lymphovascular and perineural structures, but also to lymph nodes or distant organs. The function of these immune cells is relevant for the recurrence risk and patient survival, even in very small tumours. Galon und colleagues developed a simple „immune score" method, which may be of clinical value for the identification of high-risk patients.