De Filippi R, Cucchiara G, Prete S P, Marini S, Ricci F, Nunziata C, Turriziani M, Bonmassar E, Fuggetta M P, De Vecchis L
Department of Experimental Medicine and Biochemical Sciences, 2nd University of Rome, Italy.
Ann Oncol. 1991 Nov-Dec;2(10):759-64. doi: 10.1093/oxfordjournals.annonc.a057860.
Twelve patients with metastatic colorectal cancer received alternating cycles of low immunomodulating doses of alpha-IFN + 5-Fluorouracil (5-FU) or 5-FU alone. Hematological, biochemical and physical evaluation showed that both treatment cycles were well tolerated. However, transient fever and moderate flu-like symptoms were observed following alpha-IFN administration. Treatment with 5-FU alone produced long-lasting inhibition of CD8+ T lymphocytes, but did not depress NK activity (NKA). Combined treatment with alpha-IFN produced a short-term increase of NKA and antagonized the effect of 5-FU on CD8+ cells on day 5 of the cycle. Parallel studies on in vitro models showed antiproliferative effects of 5-FU on PHA-stimulated MNC and confirmed the preferential inhibition of CD8+ cells. Pretreatment with alpha-IFN did not reverse the effect of 5-FU on CD8+ lymphocytes, but partially protected MNC from the toxic effects of the drug. This was presumably due to the cytostatic effects induced by alpha-IFN on MNC before exposure to the cycle-specific antineoplastic agent. This investigation suggests that alpha-IFN could play a positive role in immuno-chemotherapy of colorectal cancer through multiple mechanisms not entirely related to direct antitumor effects of the agent.
12例转移性结直肠癌患者接受了低免疫调节剂量的α-干扰素与5-氟尿嘧啶（5-FU）交替循环治疗或单纯5-FU治疗。血液学、生化和体格检查表明，两个治疗周期的耐受性均良好。然而，在给予α-干扰素后观察到短暂发热和中度流感样症状。单纯5-FU治疗可长期抑制CD8+T淋巴细胞，但不降低自然杀伤活性（NKA）。α-干扰素联合治疗可使NKA短期升高，并在周期第5天拮抗5-FU对CD8+细胞的作用。体外模型的平行研究显示，5-FU对PHA刺激的单核细胞有抗增殖作用，并证实其对CD8+细胞有优先抑制作用。α-干扰素预处理不能逆转5-FU对CD8+淋巴细胞的作用，但可部分保护单核细胞免受药物的毒性作用。这可能是由于α-干扰素在单核细胞暴露于周期特异性抗肿瘤药物之前诱导了细胞生长抑制作用。本研究提示，α-干扰素可能通过多种机制在结直肠癌的免疫化疗中发挥积极作用，这些机制并不完全与该药物的直接抗肿瘤作用相关。
