Abstract
BackgroundImmunotherapy has emerged as a significant strategy to treat numerous tumors. The positive response to immunotherapy depends on the dynamic interaction between tumor cells and infiltrating lymphocytes in the tumor microenvironment (TME). Pyroptosis, inflammation-induced cell death, is intricately associated with several tumors. However, the relationship between pyroptosis and clinical prognosis, immune cell infiltration, and immunotherapy effect is unclear in breast cancer (BRCA).MethodsWe comprehensively evaluated 33 pyroptosis-related genes and systematically assessed the relationship between pyroptosis and tumor progression, prognosis, and immune cell infiltration. The PyroptosisScore was used to quantify the pyroptosis pattern of a single tumor patient. We then assessed their values for predicting prognoses and therapeutic responses in BRCA.ResultsThree different modes of PyroptosisClusters were determined. The characteristics of TME cell infiltration in these three PyroptosisClusters were highly consistent with three immunophenotypes of tumors, including immune-excluded, immune-inflamed, and immune-desert phenotypes. Comprehensive bioinformatics analysis revealed that patients with a low PyroptosisScore had higher immune checkpoint expression, higher immune checkpoint inhibitor (ICI) scores, increased immune microenvironment infiltration, and were more sensitive to immunotherapy than those with a high PyroptosisScore.ConclusionsOur findings revealed the crucial role of pyroptosis in maintaining the diversity and complexity of TME. Pyroptosis is closely related to tumor progression, tumor prognosis, and immunotherapy response. Evaluating the PyroptosisScore of a single tumor can assist in understanding the characteristics of TME infiltration and lead to the development of more effective immunotherapy strategies.
Highlights
Immunotherapy has emerged as a significant strategy to treat numerous tumors
We comprehensively evaluated the expression of pyroptosisrelated genes and their effect on the progression, malignancy, prognosis, and immune response of breast cancer (BRCA)
Gene expression profiles and clinical information were downloaded from the Cancer Genome Atlas (TCGA) and Abbreviations: BRCA, Breast cancer; tumor microenvironment (TME), Tumor microenvironment; immune checkpoint blocking (ICB), Immune Checkpoint Blocking; ICI, immune checkpoint inhibitor; fragments per kilobase million (FPKM), Fragments per Kilobase Million; transcripts per million (TPM), Transcripts per Million; gene ontology (GO), Gene ontology; KEGG, Kyoto Encyclopedia of Genes and Genomes; DEG, Differential gene; CNV, copy number variations
Summary
Immunotherapy has emerged as a significant strategy to treat numerous tumors. The positive response to immunotherapy depends on the dynamic interaction between tumor cells and infiltrating lymphocytes in the tumor microenvironment (TME). The relationship between pyroptosis and clinical prognosis, immune cell infiltration, and immunotherapy effect is unclear in breast cancer (BRCA). The mortality rate of BRCA has been drastically reduced recently due to the development of more effective and superior medical diagnostic and imaging techniques, the prognosis of patients with BRCA is still poor [4, 5]. The tumor microenvironment (TME) has been implicated in the occurrence and development of BRCA [6,7,8]. Studies have shown infiltration of numerous inflammatory cells in BRCA; e.g., the density of CD8+ T cells is highly related to the immune escape of BRCA. Compared with other cancers, little work has been done toward the development of immunotherapy for BRCA
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