The effect of 5-fluorouracil and alpha interferon and 5-fluorouracil and leucovorin on cellular anti-tumour immune responses in patients with advanced colorectal cancer

Abstract

SaryInterferon (IFN-a) enhances the activity of 5-fluorouracil (5-FU) in the treatment of advanced colorectal cancer although the mechanism is not understood. We have investigated the effect of this combination on cellular immunity and compared this with standard therapy of 5-FU/L-leucovorin, in Poon et al., 1989).The mechanism by which IFN-a modulates the activity of 5-FU is unknown. In vitro cytoxicity studies using gastrointestinal cell lines how that interferon acts synergistically with 5-FU (Wadler et al., 1990). It may be acting as an antiproliferative agent, either by biochemically modulating the effect of 5-FU or by some other mechanism. While other reports suggest that interferon alters the pharmacokinetics of 5-FU (Grem et al., 1991;Schuller et al., 1992) we have demonstrated that the steady-state plasma levels of 5-FU during two 5-day infusions, with and without IFN-a in the same patients, showed no significant differences (Pitman et al., 1993).Another possibility is that IFN-a may be acting through an immunological mechanism. It is known to augment natural killer (NK) cell activity, and it up-regulates expression of both class I MHC antigen and tumour-associated antigen in tumours (Trincheri et al., 1985), perhaps with the effect of making the tumour more immunogenic. However, little is known about the immunological effects of 5-FU when combined with IFN-a. We have, therefore, studied the effects of this combination on several aspects of cellular immune function in patients with advanced colorectal cancer. The results are compared with those of a control group treated with the conventional therapy of 5-FU and L-leucovorin. Materials and methods PatientsTwenty-four patients were studied, 15 male and nine female. The mean ages were 58 (range 27-76) for the control group and 60 (42-78) for those receiving 5-FU with IFN-a. All patients had histologically proven metastatic colorectal cancer, the sites of metastases being shown in Table I (Erlichman et al., 1988). There were no differences between the study and control groups in terms of age, sex, burden or distribution of disease or performance status.

An Autophagy-Related Gene Signature Predicts Prognosis of Early Stage Colorectal Cancer

“…GSEA revealed that the ATG signature included genes that were robustly involved in multiple immune/ in ammatory pathways including IL6/JAK/STAT3, IL2/STAT5, IFN-α, IFN-γ, TNF-α/NF-κB, and the in ammatory response presented a particular relation to CRC proliferation or prognosis as previous studies revealed [21][22][23][24][25]. As our ndings suggested that a high autophagy risk score correlated with the downregulation of these immune/ in ammatory pathways, we speculated that autophagy might play a role in CRC tumorigenesis and tumor proliferation via an anti-immune/ anti-in ammatory response.…”

Identification of an Autophagy-Related Gene Signature for the Prediction of Prognosis in Early-Stage Colorectal Cancer

“…GSEA revealed that the ATG signature included genes that were robustly involved in multiple immune/inflammatory pathways including IL6/JAK/STAT3, IL2/STAT5, IFN-α, IFN-γ, and TNF-α/NF-κB, and the inflammatory response presented a particular relation to CRC proliferation or prognosis as previous studies revealed ( Nichols et al, 1994 ; Eguchi et al, 2003 ; De Simone et al, 2015 ; Park et al, 2017 ; Giordano et al, 2019 ). As our findings suggested that a high autophagy risk score correlated with the downregulation of these immune/inflammatory pathways, we speculated that autophagy might play a role in CRC tumorigenesis and tumor proliferation via an anti-immune/anti-inflammatory response.…”

An Autophagy-Related Gene Signature Predicts Prognosis of Early Stage Colorectal Cancer

“…GSEA revealed that the ATG signature included genes that were robustly involved in multiple immune/ in ammatory pathways including IL6/JAK/STAT3, IL2/STAT5, IFN-α, IFN-γ, TNF-α/NF-κB, and the in ammatory response presented a particular relation to CRC proliferation or prognosis as previous studies revealed [21][22][23][24][25].…”