Department of Medical Oncology, ASST Monza, via Pergolesi, Monza, Italy.
School of Medicine and Surgery, Bicocca Bioinformatics Biostatistics and Bioimaging B4 Center, University of Milano - Bicocca, via Cadore, Monza, Italy.
BMC Cancer. 2021 Mar 10;21(1):260. doi: 10.1186/s12885-021-07960-z.
Tumor microenvironment (TME) is a dynamic setting and changes in TILs and their subpopulations are potential candidates to influence the metastatic process. Aim of this pilot study is to describe the changes occurring between primary breast cancers and their paired metastases in terms of TILs composition. To assess if these changes influence the process of metastasis development, we used a control group of patients.
We retrospectively identified 18 Luminal patients, for whom primary and metastatic tissue were available (cases) and 18 paired-matched patients (controls), not relapsed after at least 9 years of follow-up, and we quantified TILs and their composition (i.e. T CD8+ and CD4+/FOXP3+). The presence of TILs was defined as ≥10%.
Our results showed that the microenvironment composition of relapsed patients was poor of TILs (median = 5%, I-III quartiles = 0.6-5%), CD8+ (2.5%, 0-5%) and CD4+/FOXP3 + (0%, 0-0.6%) in the primary tumor. Comparable results were observed in their related metastases (TILs 3.8%, 0.6-5%; CD8+ 0%, 0-1.3%; CD4+/FOXP3+ 0%,0-1.9%). On the contrary, the microenvironment in the control group was richer of TILs (5%, 5-17.5%) in comparison to cases, both in primary tumor (p = 0.035) and related metastases (p = 0.018). Although CD8+ in controls were similar to cases at primary tumor (p = 0.6498), but not at metastasis (p = 0.0223), they expressed only one part on the TILs subpopulations (p = 0.0060), while TILs in the cases at primary tumor were almost completely CD8+ (p = 0.5034).
These findings suggest that the lack of activation of immune system in the primary tumor might influence the multifactor process of cancer progression.
肿瘤微环境（TME）是一个动态的环境，TIL 及其亚群的变化可能是影响转移过程的潜在候选因素。本研究旨在描述原发性乳腺癌及其配对转移灶中 TIL 组成的变化。为了评估这些变化是否影响转移发展过程，我们使用了一组对照组患者。
我们回顾性地确定了 18 例 Luminal 患者，这些患者有原发性和转移性组织（病例）和 18 对匹配的患者（对照组），这些患者在至少 9 年的随访后没有复发，我们对 TIL 及其组成（即 T CD8+和 CD4+/FOXP3+）进行了定量分析。TILs 的存在定义为≥10%。
我们的结果表明，复发患者的微环境组成中 TILs（中位数=5%，I-III 四分位数=0.6-5%）、CD8+（2.5%，0-5%）和 CD4+/FOXP3+（0%，0-0.6%）在原发性肿瘤中含量较低。在其相关转移灶中也观察到类似的结果（TILs 3.8%，0.6-5%；CD8+0%，0-1.3%；CD4+/FOXP3+0%，0-1.9%）。相反，对照组的 TILs 在原发性肿瘤中比病例组更为丰富（5%，5-17.5%），在原发性肿瘤（p=0.035）和相关转移灶（p=0.018）中均如此。尽管对照组的 CD8+与病例组在原发性肿瘤中相似（p=0.6498），但在转移灶中不相似（p=0.0223），它们只在 TILs 亚群中表达一部分（p=0.0060），而病例组原发性肿瘤中的 TILs 几乎完全是 CD8+（p=0.5034）。
这些发现表明，原发性肿瘤中免疫系统的激活不足可能影响癌症进展的多因素过程。
