Comparison of tumor‐infiltrating lymphocytes between primary and metastatic tumors in breast cancer patients

Abstract

The presence of tumor‐infiltrating lymphocytes (TILs) is associated with favorable long‐term outcome in breast cancer. However, little is known about changes in TILs during metastatic progression. To confirm our hypothesis that malignant tumors escape from the host immune system during metastasis, we evaluated the percentage of TILs in paired samples of primary and metastatic breast tumors. We retrospectively identified 25 patients with human epidermal growth factor receptor‐2 (HER2+, n = 14) and triple negative (TN, n = 11) early breast cancer diagnosed between 1990 and 2009 at Tokai University Hospital (Isehara, Japan) and who subsequently experienced regional or distant recurrence confirmed by tumor biopsy/resection. Hematoxylin–eosin‐stained slides of these paired samples were evaluated for stromal TILs. Immunohistochemical staining was carried out using primary antibodies against CD4, CD8, Foxp3, programmed cell death ligand 1 (PD‐L1), PD‐L2, and HLA class I for characterizing the TILs and breast tumors. The percentage of TILs in the primary tumors was significantly higher (average 34.6%) than that in metastatic tumors (average 15.7%) (paired t‐test, P = 0.004) and that of CD8+ and CD4+ T cells significantly decreased from primary to metastatic tumors (paired t‐test, P = 0.008 and P = 0.026, respectively). The PD‐L1, PD‐L2, and HLA class I antibody expression changed from positive to negative and vice versa from the primary to the metastatic tumors. Tumors at first metastatic recurrence in HER2+ and TN breast cancers have a lower percentage of TILs and CD8+ and CD4+ T cells compared to primary tumors, which indicates that immune escape plays a role in tumor progression.

Heterogeneity of tumour‐infiltrating lymphocytes in breast cancer and its prognostic significance

“…Interestingly, TILs showed lower proportions and were more homogeneously distributed in recurrent tumours than in their corresponding primary tumours. This is consistent with a previous report in which lower expression of TILs in metastatic recurrences of TNBC and HER2+ BC were observed than in primary tumours . Moreover, significantly shorter post‐recurrence survival was observed in patients with recurrences with dense TILs, providing evidence that assessment of TILs in recurrent tumours can be used as a prognostic variable to predict post‐recurrence outcome.…”

Optically responsive delivery platforms: from the design considerations to biomedical applications

“…The advantages of drug delivery by lymphocytes are their migration and accumulation inside the tumour areas. Moreover, such delivery system can detect and attack metastases that are hard to be diagnosed [215,230]. Another type of lymphocytes, socalled NK cells, can more effectively attack infections and tumours [231].…”

Immunotherapy in Triple-Negative Breast Cancer: Present and Future

“…There are some considerations as to why stromal TILs were unable to correlate with benefit. TILs have been noted to be decreased in metastatic compared with early breast cancers [79]. There also appears to be a scarcity of stroma in metastatic breast cancer specimens and whether this could contribute to an inability to detect an association between stromal TILs and OS benefit is a consideration.…”