Factors within the tissue of
breast cancer (BC) may shift the polarization of CD4+ T cells towards Th2 direction. This tendency can promote
tumor development and be enhanced by the use of
tamoxifen during the treatment. Thus, the patients with low levels of
tumor-induced Th2 polarization prior to
tamoxifen treatment may better endure the immune-polarizing side effects (IPSE) of
tamoxifen and have better prognoses. Estimation of Th2 polarization status should help predict the IPSE among
tamoxifen-treated patients and guide the use of
tamoxifen among all BC patients before the
tamoxifen therapy. Here, we report profiling of differentially expressed (DE) intratumoral
cytokines as a signature to evaluate the IPSE of
tamoxifen. The DE genes of intratumoral CD4+ T cells (CD4 DEGs) were identified by gene expression profiles of purified CD4+ T cells from BC patients and validated by profiling of cultured intratumoral CD4+ T cells. Functional enrichment analyses showed a directed Th2 polarization of intratumoral CD4+ T cells. To find the factors inducing the Th2 polarization of CD4+ T cells, we identified 995 common DE genes of bulk BC tissues (BC DEGs) by integrating five independent datasets. Five DE
cytokines observed in bulk BC tissues with dysregulated receptors in the intratumoral CD4+ T cells were selected as the predictor of the IPSE of
tamoxifen. The patients predicted to suffer low IPSE (low Th2 polarization) had a significantly lower distant relapse risk than the patients predicted to suffer high IPSE in independent datasets (n = 608; HR = 4.326, P = 0.000897; HR = 2.014, P = 0.0173; HR = 2.72, P = 0.04077). Patients predicted to suffer low IPSE would benefit from
tamoxifen treatment (HR = 2.908, P = 0.03905). The DE intratumoral
cytokines identified in this study may help predict the IPSE of
tamoxifen and justify the use of
tamoxifen in BC treatment.