Oble Darryl A, Loewe Robert, Yu Ping, Mihm Martin C
Department of Pathology, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, Warren 827, Boston, MA 02114, USA.
Cancer Immun. 2009 Apr 2;9:3.
Tumors contain variable numbers of lymphocytes, referred to as tumor infiltrating lymphocytes (TILs). In melanoma, the intensity of this lymphocytic infiltrate is believed to correlate with outcome, though there is some debate about the applicability of this finding for all melanomas. Much research has gone into classifying TILs with respect to antigen receptor structure and the antigen to which melanoma-specific T cells react. However, these studies for the most part did not immunophenotype TILs, and recent data has revealed that the composition of tumoral lymphocytes is not homogenous, but rather represents varying contributions from many lymphocytic subsets. Furthermore, the function of TILs is often compromised as a result of the accumulation of immunoregulatory cells and various tumor escape mechanisms. These recent insights stress the need to collect more data on the composition and function of TIL infiltrates before definitive conclusions about the prognostic significance of TILs can be drawn. Advances in immunology have also facilitated the development of immunotherapeutic strategies, examples of which will be discussed with a special emphasis on blocking antibodies against CTLA-4, which are prototypical immunotherapeutic agents. This flurry of novel "biological" therapies will undoubtedly complicate our already incomplete understanding of TIL immunobiology as each of these agents has the potential to uniquely distort the series of immunological events which normally occur in untreated melanoma. Therefore, considerable research is needed to better elucidate the function and prognostic significance of TILs in both untreated melanoma and tumors treated with "biological" therapy.
肿瘤中含有数量不等的淋巴细胞，称为肿瘤浸润淋巴细胞（TILs）。在黑色素瘤中，这种淋巴细胞浸润的强度被认为与预后相关，尽管对于这一发现是否适用于所有黑色素瘤存在一些争议。关于根据抗原受体结构和黑色素瘤特异性T细胞反应的抗原对TILs进行分类，已经开展了大量研究。然而，这些研究大多没有对TILs进行免疫表型分析，最近的数据表明，肿瘤淋巴细胞的组成并非同质，而是代表了许多淋巴细胞亚群的不同贡献。此外，由于免疫调节细胞的积累和各种肿瘤逃逸机制，TILs的功能常常受到损害。这些最新见解强调，在得出关于TILs预后意义的明确结论之前，需要收集更多关于TIL浸润的组成和功能的数据。免疫学的进展也促进了免疫治疗策略的发展，将讨论其中的一些例子，特别强调针对CTLA-4的阻断抗体，这是典型的免疫治疗药物。这一系列新型“生物”疗法无疑会使我们对TIL免疫生物学本就不完整的理解变得更加复杂，因为这些药物中的每一种都有可能独特地扭曲未治疗黑色素瘤中正常发生的一系列免疫事件。因此，需要进行大量研究，以更好地阐明TILs在未治疗的黑色素瘤和接受“生物”治疗的肿瘤中的功能和预后意义。
