Triple-negative breast cancer (TNBC) is an aggressive and heterogeneous disease. Seven subtypes have been described based on gene expression patterns. Herein, we characterized the tumor biology and clinical behavior of the immunomodulatory (IM) subtype. Methods: Formalin-fixed paraffin-embedded tumor samples from 68 high-risk (stage III-IV) TNBC patients were analyzed through microarrays, immunohistochemistry, and DNA sequencing. Results: The IM subtype was identified in 24% of TNBC tumor samples and characterized by a higher intratumoral (intT) and stromal (strml) infiltration of FOXP3+ TILs (Treg) compared with non-IM subtypes. Further, PD-L1+ (>1%) expression was significantly higher, as well as CTLA-4+ intT and strml expression in the IM subtype. Differential expression and gene set enrichment analysis identified biological processes associated with the immune system. Pathway analysis revealed enrichment of the β-catenin signaling pathway. The non-coding analysis led to seven Long Intergenic Non-Protein Coding RNAs (lincRNAs) (6 up-regulated and 1 down-regulated) that were associated with a favorable prognosis in the TNBC-IM subtype. The DNA sequencing highlighted two genes relevant to immune system responses: CTNNB1 (Catenin β-1) and IDH1. Conclusion: the IM subtype showed a distinct immune microenvironment, as well as subtype-specific genomic alterations. Characterizing TNBC at a molecular and transcriptomic level might guide immune-based therapy in this subgroup of patients.

The Chromosome-Centric Human Proteome Project (C-HPP) is an international initiative. It aims to create a protein list expressed in human cells by each chromosomal and mitochondrial DNA to enhance our understanding of disease mechanisms, akin to the gene list generated by the Human Genome Project. Transmembrane protein 160 (TMEM160) is a member of the transmembrane proteins (TMEM) family. TMEM proteins have been implicated in cancer-related processes, including cell proliferation, migration, epithelial-mesenchymal transition, metastasis, and resistance to chemotherapy and radiotherapy. This study aimed to investigate the role of TMEM160 in non-small cell lung cancer and cervical cancer using cell lines, clinical samples, and xenograft studies. Our findings demonstrated that TMEM160 knockdown decreased the proliferation of lung and cervical cancer cell lines. We observed that TMEM160 is localized in the nucleus and cytoplasm and dynamic localization during mitosis of cancer cells and discovered a novel interaction between TMEM160 and nuclear proteins such as NUP50. Furthermore, the TMEM160 interactome was enriched in processes associated with apical junctions, xenobiotic metabolism, glycolysis, epithelial-mesenchymal transition, reactive oxygen species, UV response DNA, the P53 pathway, and the mitotic spindle. This study provides an initial understanding of the function of TMEM160 in lung and cervical cancer progression and clarifies the need to continue investigating the participation of TMEM160 in these cancers.

A Fine–Gray analysis was missing in the original version