To our knowledge, the purpose of this cohort of HER2-positive breast cancer research was to evaluate the expression of PD-L1 in stromal l infiltrating immune cells and the infiltration level of tumor infiltrating lymphocytes (TILs) and the expression of other immunological biomarkers (CD4, CD8).Our study cohort included 156 patients who were HER2-positive. The expression rate of PD-L1 in 156 HER2-positive breast cancer mesenchymal immune cells in this study was 31.4% (49/156). In this study, it was found that the expression of PD-L1 in breast cancer with HER2-positive was significantly correlated with the tumor size, Lymphovascular invasion ,TILs infiltration level, CD4 + cells and CD8 + cells TILs mainly includes different types of T lymphocytes, B lymphocytes and NK cells, among which T lymphocytes that mainly play an anti-tumor role are divided into CD4 + T cells, CD8 + T cells and regulatory T cells. The type and infiltration level of TILs are related to the prognosis of tumor patients[10–11]. In HER2-positive breast cancer, patients with high TILs infiltration levels often have a better prognosis[12]. Raphael et al.[13] reported that in breast cancer with HER2-positive, the infiltration level of TILs was positively correlated with the histological grade, that is, the higher the histological grade was, the higher the infiltration level of TILs was. It suggested that TILs infiltration level was closely related to tumor differentiation. This study found that TILs infiltration level was positively correlated with the expression of PD-L1. Some studies have indicated that TILs infiltration level affects the responsiveness of breast cancer patients with HER2-positive to neoadjuvant chemotherapy and trastuzumab[14]. Therefore, the study of related factors affecting TILs in breast cancer and intervention may help improve the anti-tumor immune function of patients, improve the clinical tumor treatment effect and improve the prognosis of patients.
For breast cancer patients receiving standardized treatment, whether PD-L1 expression is a favorable or unfavorable prognostic factor is a subject of conflicting results in the literature. Most of the published studies have involved different subtypes of breast cancer, with the exception of several studies that specifically targeted TNBC [15, 16].Reported inconsistencies may be related to evaluation methods, numerical thresholds, antibody clones, or differences in cohort composition. In our cohort, patients' DFS was significantly correlated with ttumor size, TILs, lymphovascular invasion, CD4 + cells, CD8 + cells, TIME-CD4 and TIME-CD8,, while PD-L1 expression was not significantly correlated with patients' DFS. Since PD-L1 mediates checkpoint immune escape by suppressing the immune response of tumor cells, it has been speculated that the expression of PD-L1 may be associated with poor prognosis. However, studies of breast cancer and many tumors, including lung cancer and melanoma, have shown that PD-L1 expression is associated with better prognosis [17–19].Therefore, the expression of PD-L1 in most cases may reflect a strong primary immune response rather than a successful immune escape. One possible explanation for these findings is that the expression of PD-L1 in immune cells in the tumors studied was an adaptive response to a cytotoxic immune attack on tumor neoantigens, rather than PD-L1 produced by tumor cells based on a gene activation pathway[20]. This will make these tumors more sensitive to driver pathway blocking therapy (such as HER2) or checkpoint immune pathway blocking therapy. The significance of different immune response patterns and intratumoral and periatumoral patterns for checkpoint blocking therapy must await data from immunotherapy trials. The biggest limitation of this study may lie in the use of tissue chips. TAMs may not be representative, increasing the possibility of false negative results.
In this study, we analyzed for the first time the relationship between immune typing and progression-free survival in HER2-positive patients. The results showed that the type of CD8+/PD-L1 + had the best prognosis, while the type of CD8-/PD-L1 + had the worst prognosis. The TILs infiltration score was positively correlated with prognosis. There are several limitations to our study. First, the number of patients participating in this study is small, reflecting the difficulty of obtaining the right number of matched samples for such studies. Second, for IHC analysis of PD-L1 expression and CD8 + TILs, we used a relatively standardized scoring system. However, different PD-L1 scoring schemes have been used to determine the treatment of each PD-L1 inhibitor available on the market. Although there is currently a standardized interstitial CD8 + TIL scoring system, there is no standardized CD8 + TIL scoring protocol for breast cancer..
In conclusion, our data indicate that the type of CD8+/PD-L1 + and TILs infiltration levels predict the prognosis of HER2-positive breast cancer treated with standard therapy. There are several shortcomings in this study: the number of cases was small, the tissue chip had some limitations, the heterogeneity of the tumor itself and the protein loss or insensitivity caused by the wax block stored for a long time. Some results have yet to be confirmed by big data. These findings, which are supported by other studies, offer hope for predicting immune checkpoint therapy.