Introduction Colorectal cancer (CRC) is one of the commonest malignancies in men and women. Clinical staging is used to predict prognosis after resection. The interaction of the cancer with the adaptive cellular immune response plays an important role in disease pathogenesis, but this relationship may be compromised by a population of regulatory Foxp3+ CD4+ T cells (Tregs). Here, the 5 year post-operative clinical outcome was correlated with pre-operatively measured anti-tumour immune responses.
Methods Eighty patients with non-metastatic CRC, undergoing a resection with curative intent, were recruited over 24 months. CD4+ T cell responses to tumour associated antigens (CEA and 5T4) were compared to control antigens (PPD and HA). The influence of immune regulation was measured by repeating the assays after in vitro depletion of Tregs. Clinical databases were interrogated for details, including morbidity and mortality data, and the five year overall survival (OS), time to progression (TTP), and progression free survival (PFS) was calculated. These parameters were compared to the original details of pre-operative anti-tumour immune responses.
Results The most important clinical factor influencing patient outcome was the colorectal cancer itself, and hence there was no significant difference between five year OS (55%), TTP (62%) and PFS (52%). As expected the disease was most likely to recur in subjects with more advanced tumours (Duke’s C p = 0.04) and male sex. However, irrespective of the tumour stages Duke’s A-C, the most significant risk factor for tumour recurrence was the presence of anti-CEA CD4+ T cell responses, the majority of which were suppressed by Tregs (p = 0.002). The magnitude of these responses was greater in the group with disease recurrence (p = 0.004). Pre-operative responses to other antigens, including the tumour antigen 5T4, did not reflect outcome.
Conclusion The presence of pre-operative anti-CEA immune responses identifies patients most likely to experience CRC recurrence during the 5 year follow-up period. This relationship holds true irrespective of the tumour stage. This information might be used to direct adjuvant treatment strategies.
Disclosure of Interest None Declared.