Kaffenberger W, Hölzer-Müller L, Auberger T, Clasen B P, Hohlmeier G, van Beuningen D
Institute of Radiobiology, Federal Armed Forces Medical Academy, Munich.
Strahlenther Onkol. 1995 Aug;171(8):444-53.
To address the increasing demand for individualization of tumor therapy, a panel of immunological parameters was evaluated as potential early prognosticators for the outcome of treatment.
Thirty-one patients with advanced squamous cell carcinomas of the head and neck were treated either with a 2-course radiation treatment (60 to 70 Gy total dose) in combination with and subsequent to the administration of mitomycin C and 5-fluorouracil (radiochemotherapy) or with radiotherapy (2 patients) only. In 8 patients radio(chemo)therapy was preceded by surgical removal of the tumor. Before, during and after therapy, patients were immunophenotyped (in absolute numbers) and the respiratory burst function of granulocytes (polymorphonuclear [PMN] cells) was evaluated flow cytometrically.
Before treatment a reduction of T and B lymphocytes to 64% to 81% of the means of 101 controls (healthy volunteers and hematologic normal patients) was observed, absolute PMN counts were increased by 31%, whereas monocytes and natural killer cells were not influenced. The helper (TH)/suppressor-cytotoxic (Ts/c) T cell ratio was significantly elevated. The respiratory burst reaction of the majority (74%) of patients was normal. During therapy all lymphocyte populations declined further as did the PMN counts. Natural killer cells were not significantly influenced while absolute monocytes increased significantly beyond normal levels after initial depletions during each course of treatment. The helper/suppressor ratio was reduced to normal levels. Overall, treatment resulted in systemic effects at the level of leukocyte subpopulations and appeared to cause a shift of immunocompetence to a predominantly monocytic system. The deficiency in the humoral immune system could be correlated with the short survival time of most patients. Based on early effects of the treatment (after 10 Gy), an immunological outcome predictive score could be defined. A simple mathematical combination of the changes of B and Ts/c cells (after 10 Gy vs. 0 Gy) together with the respiratory burst reaction of PMN prior to treatment allowed retrospectively to classify correctly 90% (17/19) of patients as survivors (> 120 weeks) or early deaths (< 96 weeks; p < 0.01).
Single individual immunological data were not able to function as prognosticators for longer survival after therapy, but a combination of 3 parameters measured early during radio(chemo)therapy seems to allow the identification of "sensitive" patients. In how far the tumor disease per se and/or the immunological "sensitivity" are causes of death in these patients requires further clarification.
为满足肿瘤治疗个体化需求的不断增加，对一组免疫参数进行评估，以作为治疗结果潜在的早期预后指标。
31例晚期头颈部鳞状细胞癌患者接受了如下治疗：2疗程放射治疗（总剂量60至70 Gy），联合并在给予丝裂霉素C和5-氟尿嘧啶后进行（放化疗），或仅接受放疗（2例患者）。8例患者在放（化）疗前接受了肿瘤手术切除。在治疗前、治疗期间和治疗后，对患者进行免疫表型分析（以绝对计数），并通过流式细胞术评估粒细胞（多形核[PMN]细胞）的呼吸爆发功能。
治疗前观察到T和B淋巴细胞减少至101名对照者（健康志愿者和血液学正常患者）均值的64%至81%，PMN绝对计数增加31%，而单核细胞和自然杀伤细胞未受影响。辅助性（TH）/抑制性细胞毒性（Ts/c）T细胞比值显著升高。大多数（74%）患者的呼吸爆发反应正常。治疗期间，所有淋巴细胞亚群以及PMN计数进一步下降。自然杀伤细胞未受显著影响，而在每个疗程治疗开始时单核细胞绝对计数最初减少后，显著增加至超出正常水平。辅助/抑制比值降至正常水平。总体而言，治疗导致白细胞亚群水平出现全身效应，似乎使免疫能力向以单核细胞为主的系统转变。体液免疫系统的缺陷与大多数患者的短生存期相关。基于治疗的早期效应（10 Gy后），可以定义一个免疫结果预测评分。治疗前B细胞和Ts/c细胞变化（10 Gy后与0 Gy后相比）以及PMN呼吸爆发反应的简单数学组合，能够回顾性地将90%（17/19）的患者正确分类为幸存者（>120周）或早期死亡者（<96周；p<0.01）。
单个免疫数据不能作为治疗后长期生存的预后指标，但放（化）疗早期测量的3个参数的组合似乎能够识别出 “敏感” 患者。肿瘤疾病本身和 / 或免疫 “敏感性” 在多大程度上是这些患者的死亡原因，需要进一步阐明。
