Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0006142 (breast cancer)
 160,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

[Fam-] trastuzumab deruxtecan (DS-8201a) is a HER2 (ERBB2)-targeting antibody-drug conjugate, composed of a HER2-targeting antibody and a topoisomerase I inhibitor, exatecan derivative, that has antitumor effects in preclinical xenograft models and clinical trials. Recently, [fam-] trastuzumab deruxtecan was reported to enhance antitumor immunity and was beneficial in combination with an anti-PD-1 antibody in a mouse model. In this study, the antitumor effect of [fam-] trastuzumab deruxtecan in combination with an anti-CTLA-4 antibody was evaluated. [Fam-] trastuzumab deruxtecan monotherapy had antitumor activity in an immunocompetent mouse model with EMT6 human HER2-expressing mouse breast cancer cells (EMT6-hHER2). [Fam-] trastuzumab deruxtecan in combination with the anti-CTLA-4 antibody induced more potent antitumor activity than that by monotherapy with either agent. The combination therapy increased tumor-infiltrating CD4+ and CD8+ T cells in vivo. Mechanistically, cured mice with treatment of [fam-] trastuzumab deruxtecan and an anti-CTLA-4 antibody completely rejected EMT6-mock cells similar to EMT6-hHER2 cells, and splenocytes from the cured mice responded to both EMT6-hHER2 and EMT6-mock cells as measured by interferon-gamma release. Taken together, these results indicate that antitumor immunity is induced by [fam-] trastuzumab deruxtecan and is facilitated in combination with anti-CTLA-4 antibody.
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PMID:[Fam-] trastuzumab deruxtecan (DS-8201a)-induced antitumor immunity is facilitated by the anti-CTLA-4 antibody in a mouse model. 3157 81

Immune response and immunotherapy play important roles in triple-negative breast cancer (TNBC). However, it is difficult to judge whether cancer is "immune-inactivated" or "immune-activated" by the carcinoma itself. The immune reaction of the microenvironment or the host to the tumor might be more informative. We assumed that clinically enlarged but pathologically negative regional lymph nodes served as an indicator for early immune response to tumors. First, we identified women with pN0 breast cancer disease from the current Surveillance, Epidemiology, and End Results database, and we compared the cN1 patients of breast cancer-specific survival (BCSS) with cN0 patients. Then, we extracted total RNA from 36 paired large (defined as minimum diameter more than 15 mm in size) and small lymph nodes (defined as maximum diameter less than 5 mm in size) from 12 TNBC, 12 HER2-enriched, and 12 luminal-like patients and performed RNA sequencing to explore the gene expression and cellular landscape of large nodes compared to small ones. Among 692 women with pathologically confirmed node-negative disease, cN1 patients unexpectedly had a better BCSS compared with cN0 in TNBC (adjusted hazard ratio 0.148, 95% CI, 0.040-0.546, P = 0.004) but not in other subtypes. Further transcriptome sequencing of 12 paired enlarged and small negative nodes from TNBC patients revealed that increased immune activation signaling (e.g., interferon-gamma response pathways) and abundant immune cells (activated dendritic cells, CD4+ and CD8+ T-cells) were more frequently observed in enlarged nodes. Our data implied that early immune activation in regional lymph nodes in TNBC might affect survival.
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PMID:Immune-Activated Regional Lymph Nodes Predict Favorable Survival in Early-Stage Triple-Negative Breast Cancer. 3316 1


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