Wang Kai, Shen Tiansheng, Siegal Gene P, Wei Shi
Department of Pathology, the University of Alabama at Birmingham, Birmingham, AL 35249-7331.
Department of Pathology, the University of Alabama at Birmingham, Birmingham, AL 35249-7331.
Hum Pathol. 2017 Nov;69:110-117. doi: 10.1016/j.humpath.2017.09.012. Epub 2017 Oct 6.
Compelling evidence has demonstrated the prognostic value of tumor-infiltrating lymphocytes (TILs), especially in triple-negative breast cancer (TNBC). However, only a limited number of studies to investigate the importance of the subsets of T cells in TILs have been carried out, less so the significance of the location of these TILs. In this study, we explored in a cohort of 42 consecutive TNBC cases the prognostic significance of TIL subsets at the tumor-host interface (within 1 high-power field [0.5 mm] of the invasive front) and compared them with TILs within the intratumoral stroma. Given the reported importance of TILs in HER2-overexpressing breast cancer, a subset of such tumors was also included for comparison. The range was wide in both locations; nevertheless, the mean CD4 and CD8 T cell count was significantly higher at the tumor-host interface than that found within the intratumoral stroma (both P<.0001). The number of CD4 or CD8 T cells at either location was not significantly associated with distant relapse-free or overall survival. However, the CD4/CD8 ratio at the tumor-host interface was significantly associated with both relapse-free survival (hazard ratio 0.2, P=.002) and overall survival (hazard ratio 0.13, P=.002), whereas this association was not seen for the CD4/CD8 ratio within the intratumoral stroma. As expected, both tumor size and nodal status were significantly associated with survival outcomes. The findings further support the contention that TILs, as markers of regional immune escape, are of prognostic importance in TNBC progression and that the CD4/CD8 ratio of TILs at the tumor-host interface plays a distinctive role, thus appearing to be of clinical relevance.
有力证据已证明肿瘤浸润淋巴细胞(TILs)的预后价值,尤其是在三阴性乳腺癌(TNBC)中。然而,仅有有限的研究探讨了TILs中T细胞亚群的重要性,对于这些TILs位置的重要性研究则更少。在本研究中,我们在一组连续的42例TNBC病例中,探讨了肿瘤-宿主界面(浸润前沿1个高倍视野[0.5 mm]范围内)TIL亚群的预后意义,并将其与瘤内基质中的TILs进行比较。鉴于TILs在HER2过表达乳腺癌中已报道的重要性,此类肿瘤的一个亚组也被纳入进行比较。两个位置的范围都很广;然而,肿瘤-宿主界面处的平均CD4和CD8 T细胞计数显著高于瘤内基质中的计数(均P<0.0001)。任一位置的CD4或CD8 T细胞数量与远处无复发生存或总生存均无显著相关性。然而,肿瘤-宿主界面处的CD4/CD8比值与无复发生存(风险比0.2,P=0.002)和总生存(风险比0.13,P=0.002)均显著相关,而瘤内基质中的CD4/CD8比值则未观察到这种相关性。正如预期的那样,肿瘤大小和淋巴结状态均与生存结果显著相关。这些发现进一步支持了这样的观点,即TILs作为局部免疫逃逸的标志物,在TNBC进展中具有预后重要性,且肿瘤-宿主界面处TILs的CD4/CD8比值发挥着独特作用,因此似乎具有临床相关性。