Center of Surgical and Molecular Tumor Pathology, National Institute of Oncology, 7-9. Ráth György u., Budapest 1122, Hungary.
Cancer Immunol Immunother. 2011 Dec;60(12):1729-38. doi: 10.1007/s00262-011-1071-x. Epub 2011 Jul 21.
Studies on the prognostic importance of tumor-infiltrating lymphocytes have mainly focused on T cells, while little is known about the role of tumor-infiltrating B lymphocytes. We investigated the prevalence of CD20(+) B cells by immunohistochemistry in primary melanoma samples of 106 patients and analyzed in relation to clinicopathological parameters and patients' survival. The majority of samples contained a significant amount of B lymphocytes, predominantly dispersed in the stroma surrounding tumor deposits (mean peritumoral and intratumoral densities: 178.7 ± 156.1 vs. 4.9 ± 6.9 cells/mm², respectively). B cells organized in follicle-like aggregates were also observed in 26% of the samples. B-cell density correlated with that of activated (CD25(+) or OX40(+)) T lymphocytes. Infiltration by CD20(+) lymphocytes did not correlate with tumor thickness, while the presence of B-cell aggregates was observed more frequently in thick melanomas. On the other hand, B-cell infiltration was more pronounced in nonmetastatic or lymph node metastatic tumors, compared to visceral metastatic ones. Accordingly, high number of these cells provided significant survival advantage (P = 0.0391 and P = 0.0136 for intra- and peritumoral infiltration, respectively). Furthermore, combination of peritumoral B-cell density with the number of activated T lymphocytes identified patient subgroups with different disease outcome, which was most favorable in the case of high density, while very poor in the case of low density of both cell types. Multivariate survival analysis identified tumor thickness and CD20(+)/OX40(+) cell density combination as significant independent prognostic factors. Taken together, our results show correlation between low number of CD20(+) B lymphocytes and melanoma progression, indicating a possible role of tumor-infiltrating B cells in antitumoral immune response. It was also reflected in better outcome of the disease since the density of B lymphocytes alone as well as in combination with that of activated T cells proved of prognostic importance in patients with malignant melanoma.
关于肿瘤浸润淋巴细胞预后重要性的研究主要集中在 T 细胞上，而关于肿瘤浸润 B 淋巴细胞的作用知之甚少。我们通过免疫组织化学法检测了 106 例原发性黑色素瘤样本中 CD20(+)B 细胞的流行情况，并分析了其与临床病理参数和患者生存的关系。大多数样本含有大量 B 淋巴细胞，主要分布在肿瘤沉积物周围的基质中（肿瘤周围和肿瘤内的平均密度分别为 178.7 ± 156.1 个/平方毫米和 4.9 ± 6.9 个/平方毫米）。在 26%的样本中还观察到 B 细胞呈滤泡样聚集。B 细胞密度与活化的（CD25(+)或 OX40(+)）T 淋巴细胞密度相关。B 细胞浸润与肿瘤厚度无关，而 B 细胞聚集在厚的黑色素瘤中更为常见。另一方面，与内脏转移瘤相比，B 细胞浸润在非转移性或淋巴结转移性肿瘤中更为明显。因此，这些细胞数量较多可显著提高生存率（肿瘤内和肿瘤周围浸润的 P 值分别为 0.0391 和 0.0136）。此外，将肿瘤周围 B 细胞密度与活化 T 淋巴细胞数量相结合，可确定具有不同疾病结局的患者亚组，其中 B 细胞密度高时预后最佳，而两种细胞类型密度均低时预后最差。多变量生存分析确定肿瘤厚度和 CD20(+)/OX40(+)细胞密度组合是独立的预后因素。总之，我们的结果表明，CD20(+)B 淋巴细胞数量少与黑色素瘤进展相关，表明肿瘤浸润 B 细胞可能在抗肿瘤免疫反应中发挥作用。这也反映在疾病的转归较好上，因为 B 淋巴细胞的密度，以及与活化 T 细胞的密度相结合，在恶性黑色素瘤患者中被证明具有预后意义。
