List A F, Spier C M, Miller T P, Grogan T M
Department of Internal Medicine, University of Arizona College of Medicine, Tucson.
Leukemia. 1993 Mar;7(3):398-403.
Tumor-infiltrating T-lymphocytes (T-TIL) are putative mediators of tumor containment that exhibit unique specificity for autologous tumor cells. The magnitude of T-TIL response in biopsy specimens from patients with B-cell lymphoma has been suggested as an independent predictor of clinical outcome. Since recognition of tumor antigens may occur in association with major histocompatibility complex (MHC) molecules, effective T-TIL tumor immunosurveillance may be limited by either failure to express MHC-encoded recognition structures and/or host T-cell immunocompetence. To further delineate T-cell immunoregulation in B-cell lymphoma, we assessed T-TIL fraction and tumor expression of invariant class I and class II HLA determinants by immunohistochemistry in biopsy specimens. Two distinct clinical cohorts of B-cell lymphoma were investigated to delineate pathogenetic differences in T-TIL response. One group, representing immunodeficient and transplant-related lymphomas, comprised 18 patients with AIDS- or allograft-related lymphoma. The second group comprised 83 consecutive cases of sporadic diffuse large cell (DLCL) lymphoma. Median CD8+ T-TIL was significantly lower (4.9% versus 12.7%) among immunodeficiency-associated lymphoma and the frequency of cases with low (< 6%) CD8+ T-TIL greater (76% versus 23%) (p < 0.0001). None of the immunodeficiency-associated lymphomas demonstrated non-polymorphic HLA loss. Absence of one or more class I or II HLA determinants was found in 13 out of 19 (68%) sporadic DLCL specimens with low CD8+ T-TIL, compared to 20% of cases with higher T-TIL fraction (p = 0.0004). These findings implicate impaired host immunosurveillance in deficient T-TIL response in immunodeficiency-associated B-cell lymphoma, whereas low T-TIL in sporadic cases of DLCL relates to tumor loss of HLA determinants. Strategies to modulate tumor HLA expression or augment antitumor response merit investigation in patients with B-cell lymphoma.
肿瘤浸润性T淋巴细胞（T-TIL）被认为是肿瘤抑制的介质，对自体肿瘤细胞表现出独特的特异性。B细胞淋巴瘤患者活检标本中T-TIL反应的程度已被认为是临床结果的独立预测指标。由于肿瘤抗原的识别可能与主要组织相容性复合体（MHC）分子相关，有效的T-TIL肿瘤免疫监视可能会受到无法表达MHC编码的识别结构和/或宿主T细胞免疫能力的限制。为了进一步阐明B细胞淋巴瘤中的T细胞免疫调节，我们通过免疫组织化学评估了活检标本中T-TIL分数以及不变的I类和II类HLA决定簇的肿瘤表达。研究了两个不同的B细胞淋巴瘤临床队列，以阐明T-TIL反应中的致病差异。一组代表免疫缺陷和移植相关淋巴瘤，包括18例艾滋病或同种异体移植相关淋巴瘤患者。第二组包括83例连续的散发性弥漫性大细胞（DLCL）淋巴瘤病例。免疫缺陷相关淋巴瘤中CD8 + T-TIL的中位数显著较低（4.9%对12.7%），CD8 + T-TIL低（<6%）的病例频率更高（76%对23%）（p < 0.0001）。免疫缺陷相关淋巴瘤均未显示非多态性HLA缺失。在19例CD8 + T-TIL低的散发性DLCL标本中有13例（68%）发现一种或多种I类或II类HLA决定簇缺失，而T-TIL分数较高的病例中这一比例为20%（p = 0.0004）。这些发现表明，免疫缺陷相关B细胞淋巴瘤中T-TIL反应不足与宿主免疫监视受损有关，而散发性DLCL病例中T-TIL低与肿瘤HLA决定簇缺失有关。调节肿瘤HLA表达或增强抗肿瘤反应的策略值得在B细胞淋巴瘤患者中进行研究。
