Abstract
The tumor microenvironment (TME) interacting with the malignant cells plays a vital role in cancer development. Herein, we aim to establish and verify a scoring system based on the characteristics of TME cells for prognosis prediction and personalized treatment guidance in patients with triple-negative breast cancer (TNBC). 158 TNBC samples from The Cancer Genome Atlas (TCGA) were included as the training cohort, and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) (N = 297), as well as GSE58812 (N = 107), were included as the validation cohort. The enrichment scores of 64 immune and stromal cells were estimated by the xCell algorithm. In the training cohort, cells with prognostic significance were found out using univariate Cox regression analysis and further applied to the random survival forest (RSF) model. Based on the scores of M2 macrophages, CD8+ T cells, and CD4+ memory T cells, a risk scoring system was constructed, which divided TNBC patients into 4 phenotypes (M2low, M2highCD8+ThighCD4+Thigh, M2highCD8+ThighCD4+Tlow, and M2highCD8+Tlow). Furthermore, types 1 and 2 patients were merged into the low-risk group, while types 3 and 4 patients were in the high-risk group. The low-risk group had superior survival outcomes than the high-risk one, which was further confirmed in the validation cohort. Moreover, in the low-risk group, immune-related pathways were significantly enriched, and a higher level of antitumoral immune cells and immune checkpoint molecules, including PD-L1, PD-1, and CTLA-4, could be observed. Additionally, consistent results were achieved in the SYSUCC cohort when the scoring system was applied. In summary, this novel scoring system might predict the survival and immune activity of patients and might serve as a potential index for immunotherapy.
Highlights
Female breast cancer has become the most commonly diagnosed cancer worldwide in 2020 [33]
The contents of 64 immune and stromal cells in the tumor microenvironment (TME) of triple-negative breast cancer (TNBC) were calculated through the xCell algorithm
The log-rank test of overall survival (OS) showed consistent results that higher scores of CD4+ memory T cells, CD8+ T cells, and Th2 cells were associated with better prognosis, while M2 macrophages, endothelial cells, and mv endothelial cells did the opposite
Summary
Female breast cancer has become the most commonly diagnosed cancer worldwide in 2020 [33]. The Impassion130 trial showed the addition of PD-L1 inhibitor atezolizumab to first-line nab-paclitaxel significantly improved progression-free survival (PFS) and overall survival (OS) in PD-L1-positive patients [30]. The KEYNOTE-355 trial reported that in PD-L1-positive TNBC, the PD-1 inhibitor pembrolizumab combined with first-line chemotherapy could significantly increase the benefit of PFS [11]. The most recent Impassion131 trial failed to exhibit the benefit of atezolizumab combined with paclitaxel even in PD-L1-positive patients [14]. The disparity in the benefits of ICIs neoadjuvant administration was demonstrated in the earlystage TNBC Both KEYNOTE-522 trial and Impassion trial showed the combination ICIs and chemotherapy increased pathological complete response (pCR) rates, while the NeoTRIPaPDL1 phase III trial failed to show any pCR improvement when atezolizumab was added to neoadjuvant chemotherapy [1, 14]
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