Tilden A B, Balch C M
Surgery. 1981 Jul;90(1):77-84.
Lymphocyte responses to the mitogens concanavalin A (Con A) and phytohemagglutinin (PHA) are important in vitro parameters of immunocompetence in cancer patients. The tempo and intensity of this response is regulated by monocytes. We found that the blood lymphocyte response to one or both of these mitogens was significantly depressed in 32 of 33 melanoma patients compared to 29 normal control subjects. However, these responses were significantly enhanced when the drug indomethacin, a prostaglandin synthetase inhibitor, was added to cultures of peripheral blood mononuclear cells (PBMCs) from the melanoma patients, but not from the normal control subjects. For example, at a 1 microgram/ml dose of Con A, the mean response of melanoma patients increased from 56% to 81% of the normal mean response, whereas at 20 micrograms/ml PHA the mitogen response increased from 57% to 77% of normal when PMBC were incubated with indomethacin (P less than 0.001). Overall, indomethacin enhanced the mitogen responses of melanoma patients by 35% to 85%, whereas indomethacin increased the response in normal subjects by only 5% to 15%. The mitogen response of monocyte-depleted ER+ lymphocytes for melanoma patients was equivalent to that of normal control subjects, and there was no enhancement of this response in the presence of indomethacin. This suggests that the abnormality was due to an altered function of immunoregulatory monocytes. The enhancement by indomethacin in melanoma patients was not significantly influenced by their stage of disease, age, or the proportion of blood monocytes. The decreased levels of cellular immunocompetence in these melanoma patients, as measured by their lymphocyte proliferative responses to mitogens, therefore appears to be associated with an abnormality in monocyte function that is partially corrected by indomethacin.
淋巴细胞对促有丝分裂原刀豆球蛋白A（Con A）和植物血凝素（PHA）的反应是癌症患者免疫能力的重要体外参数。这种反应的节奏和强度由单核细胞调节。我们发现，与29名正常对照受试者相比，33名黑色素瘤患者中有32名对这两种促有丝分裂原中的一种或两种的血液淋巴细胞反应明显降低。然而，当将前列腺素合成酶抑制剂消炎痛添加到黑色素瘤患者外周血单个核细胞（PBMC）的培养物中时，这些反应会显著增强，但正常对照受试者的培养物中则不会。例如，在1微克/毫升剂量的Con A下，黑色素瘤患者的平均反应从正常平均反应的56%增加到81%，而在20微克/毫升PHA时，当PMBC与消炎痛一起孵育时，促有丝分裂原反应从正常的57%增加到77%（P小于0.001）。总体而言，消炎痛使黑色素瘤患者的促有丝分裂原反应增强了35%至85%，而消炎痛仅使正常受试者的反应增加了5%至15%。黑色素瘤患者单核细胞耗竭的ER+淋巴细胞的促有丝分裂原反应与正常对照受试者相当，并且在存在消炎痛的情况下该反应没有增强。这表明异常是由于免疫调节单核细胞功能改变所致。消炎痛对黑色素瘤患者的增强作用不受其疾病阶段、年龄或血液单核细胞比例的显著影响。因此，通过淋巴细胞对促有丝分裂原的增殖反应测量的这些黑色素瘤患者细胞免疫能力的降低，似乎与单核细胞功能异常有关，而消炎痛可部分纠正这种异常。
