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The presence of tumor‐infiltrating lymphocytes ( TIL s) is associated with favorable long‐term outcome in breast cancer. However, little is known about changes in TIL s during metastatic progression. To confirm our hypothesis that malignant tumors escape from the host immune system during metastasis, we evaluated the percentage of TIL s in paired samples of primary and metastatic breast tumors. We retrospectively identified 25 patients with human epidermal growth factor receptor‐2 ( HER 2 + , 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 TIL s. Immunohistochemical staining was carried out using primary antibodies against CD 4, CD 8, Foxp3, programmed cell death ligand 1 ( PD ‐L1), PD ‐L2, and HLA class I for characterizing the TIL s and breast tumors. The percentage of TIL s 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 CD 8 + and CD 4 + 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 HER 2 + and TN breast cancers have a lower percentage of TIL s and CD 8 + and CD 4 + T cells compared to primary tumors, which indicates that immune escape plays a role in tumor progression.
Ogiya et al. (Thu,) studied this question.