Paradoxical effects of 5-FU/folinic acid on lymphokine-activated killer (LAK) cell induction in patients with colorectal cancer

Abstract

Summary The effects of treatment with 5-FU/folinic acid on interleukin-2 related lymphocyte responses was investigated in 21 patients with advanced colorectal cancer. The treatment was not suppressive of IL-2 related lymphocyte responses. Furthermore, at certain time points in the treatment cycles the capacity to generate lymphokine-activated killer (LAK) cells from the peripheral blood mononuclear cells of these patients was significantly augmented above that observed prior to treatment. These results provide a logical basis for the design of regimens which combine two approaches, each of low individual therapeutic efficacy, to treat patients with advanced colorectal cancer in the hope of increasing clinical response rates.

Natural killer cells and cancer

“…227 In patients with advanced renal cell carcinoma, overall response rates of 14% to 20% have been obtained following rIL-2 therapy,'282229 with a median duration of 357 days for partial and 926 days for complete responders. 215 However, much lower responses have been obtained in other solid tumors, e.g., colorectal ~ancer.2~' IL-2, in combination with cells with LAK activity, has been shown to result in the regression of lung, liver, and subdermal metastases of murine Infusion of autologous in vitro generated cells with LAK activity, in combination with rIL-2, has also been used to treat patients with disseminated cancer. 233 The responses of various types of tumors to rIL-2, alone or in combination with cells with LAK activity, have been extensively reviewed and are outside the scope of this present reHowever, current evidence suggests that the addition of cells with LAK activity has a marginal benefit, if any, when used with rIL-2.226*2'9 In melanoma patients, there was a trend of increased survival in patients receiving rIL-2 and cells with LAK activity, compared with rIL-2 rIL-2 has also been used in conjunction with TILs in patients with melanoma, resulting in objective responses in a third of the patients."'…”

Effect of 5‐fluorouracil on interleukin‐1 and interleukin‐2 receptor expression

“…Recent studies have shown that the many anti cancer drugs including 5-Fluorouracil can enhance the immune responses such as increasing the IL-2 expression and in generation of lymphokine activated killer like cells (2). In order to study the mechanism of immunomodulation by 5-Fluorouracil, here we report the effect of this drug on the expression of IL-I, IFN-7 and on IL-2 receptor.…”