Shabtai Moshe, Slanetz Charles A, Ye Hui, Waltzer Wayne C, Malinowski Kazimierz
Sackler School of Medicine, Tel Aviv University & Department of Surgery and Transplantation, Sheba Medical Center.
Harefuah. 2002 Oct;141(10):862-4, 932.
Tumor infiltrating lymphocytes (TIL) in colorectal cancer are a manifestation of local, cell mediated immune response to the malignant tumor. Tumor progression is due to impairment of the host ability to control tumor growth. Several studies suggested possible causes for such impairment, however, the precise factor(s) underlying such malfunction is uncertain.
To compare the possible effects of colorectal cancer (CRC) and normal colonic mucosa extracts on lectin induced blastogenesis of the same patients' peripheral blood lymphocytes (PBL) proliferation.
CRC and normal mucosa extracts were obtained from 3 patients undergoing curative surgery for colon adenocarcinoma. Proliferation assays used PBL from the CRC patients, incubated with Concanavalin A (ConA) and Phytohemoglobin (PHA) in the presence of CRC or normal mucosa extract and in medium alone. Proliferation was measured by H3 Thymidine incorporation following 48 hours on incubation.
Exposure of ConA induced PBL proliferation assay to CRC extract yielded a 98.7% inhibition measured by counts/minute (cpm) of incorporated H3 Thymidine compared to normal colonic mucosa extract (1,214 +/- 594 cpm vs. 95,335 +/- 6,997 cpm respectively, p = 0.0018). PHA stimulated proliferation exposed to CRC extract showed a 99.7% decrease in blastogenic activity compared to normal mucosa extract (362 +/- 175 cpm vs. 62,375 +/- 16,591 cpm respectively, p = 0.0234).
These preliminary results suggest that CRC extract contain factor(s) capable of profoundly inhibiting lectin induced proliferation of PBL. Shedding of suppressor substances may be one of the possible mechanisms by which the tumor evades the effector arm of the cell-mediated immune response. Characterization of such factors may aid in intratumor, local and systemic cellular immune response reconstitution.
结直肠癌中的肿瘤浸润淋巴细胞(TIL)是机体对恶性肿瘤的局部细胞介导免疫反应的一种表现。肿瘤进展是由于宿主控制肿瘤生长能力受损所致。多项研究提出了导致这种损害的可能原因,然而,这种功能失调的确切因素尚不确定。
比较结直肠癌(CRC)和正常结肠黏膜提取物对同一患者外周血淋巴细胞(PBL)增殖的凝集素诱导的母细胞化的可能影响。
从3例接受结肠癌根治性手术的患者中获取CRC和正常黏膜提取物。增殖试验使用CRC患者的PBL,在CRC或正常黏膜提取物存在以及单独培养基中与伴刀豆球蛋白A(ConA)和植物血凝素(PHA)一起孵育。孵育48小时后通过³H胸苷掺入法测量增殖情况。
与正常结肠黏膜提取物相比,ConA诱导的PBL增殖试验暴露于CRC提取物时,通过掺入³H胸苷的计数/分钟(cpm)测量显示抑制率为98.7%(分别为1,214±594 cpm和95,335±6,997 cpm,p = 0.0018)。与正常黏膜提取物相比,暴露于CRC提取物的PHA刺激的增殖显示母细胞化活性降低99.7%(分别为362±175 cpm和62,375±16,591 cpm,p = 0.0234)。
这些初步结果表明,CRC提取物含有能够深刻抑制凝集素诱导的PBL增殖的因子。抑制性物质的释放可能是肿瘤逃避细胞介导免疫反应效应臂的可能机制之一。对这些因子的表征可能有助于肿瘤内、局部和全身细胞免疫反应的重建。