The immune microenvironment of breast ductal carcinoma (DCIS) has yet to be fully explored, and the relationship of immune cells to genetic features of DCIS is unknown. We quantified tumor associated lymphocytes (TIL) and evaluated PD-L1 protein levels by immunohistochemistry in a cohort of pure DCIS (138 and 79 cases, respectively), some of which had copy number ( = 55) and mutation data ( = 20). TILs were identified in the stroma surrounding DCIS (119/138, 86%) and present at a median TIL score of 5% (range, 0%-90%). Most DCIS were negative for tumor cell PD-L1 staining (89%), but 25% of cases were positive for immune cell staining. We observed that, as in invasive breast cancer, TILs and PD-L1 positivity were significantly greater in high-grade ( = 0.002/0.035), ER-negative ( = 0.02/0.02), and -amplified tumors ( < 0.001/0.048). Comedo necrosis was significantly positively associated with TILs ( < 0.0001) but not with PD-L1. The TILs score was significantly higher in cases with mutation ( = 0.03) but not with or mutation. In the cases with copy number data, both the fraction of the genome altered and the number of telomeric imbalances were significantly positively correlated with TILs (both < 0.001). This result strongly contrasted with invasive breast cancer data, where aneuploidy was not correlated to TIL levels. Although a small cohort, our data suggest a preliminary model by which the progression of DCIS to invasive carcinoma may involve an altered relationship of tumor copy number with the immune microenvironment, possibly by the immunoediting of the tumor. .
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http://dx.doi.org/10.1158/1078-0432.CCR-17-0743 | DOI Listing |
Front Biosci (Landmark Ed)
December 2024
Mackenzie Cancer Research Group, Department of Pathology and Biomedical Science, University of Otago Christchurch, 8011 Christchurch, Aotearoa New Zealand.
Tumor-associated macrophages (TAMs) are innate immune cells that exert far reaching influence over the tumor microenvironment (TME). Depending on cues within the local environment, TAMs may promote tumor angiogenesis, cancer cell invasion and immunosuppression, or, alternatively, inhibit tumor progression via neoantigen presentation, tumoricidal reactive oxygen species generation and pro-inflammatory cytokine secretion. Therefore, TAMs have a pivotal role in determining tumor progression and response to therapy.
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December 2024
Department of Medical Biology, Faculty of Medicine, Ankara Yildirim Beyazit University (AYBU), 06800 Ankara, Turkey.
As one of the most common solid pediatric cancers, Neuroblastoma (NBL) accounts for 15% of all of the cancer-related mortalities in infants with increasing incidence all around the world. Despite current therapeutic approaches for NBL (radiotherapies, surgeries, and chemotherapies), these approaches could not be beneficial for all of patients with NBL due to their low effectiveness, and some severe side effects. These challenges lead basic medical scientists and clinical specialists toward an optimal medical interventions for clinical management of NBL.
View Article and Find Full Text PDFOnco Targets Ther
December 2024
Department of Oncology, Affiliated Dalian Third People's Hospital of Dalian Medical University, Dalian, Liaoning Province, 116033, People's Republic of China.
Immunotherapy is one of the research hotspots in colorectal cancer field in recent years. The colorectal cancer patients with mismatch repair-deficient (dMMR) or high microsatellite instability (MSI-H) are the primary beneficiaries of immunotherapy. However, the vast majority of colorectal cancers are mismatch repair proficient (pMMR) or microsatellite stability (MSS), and their immune microenvironment is characterized by "cold tumors" that are generally insensitive to single immunotherapy based on immune checkpoint inhibitors (ICIs).
View Article and Find Full Text PDFJCO Oncol Adv
December 2024
Department of Surgery, Oregon Health & Science University, Portland, OR.
Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of cancer-related deaths with a 5-year survival rate of 13%. Surgical resection remains the only curative option as systemic therapies offer limited benefit. Poor response to chemotherapy and immunotherapy is due, in part, to the dense stroma and heterogeneous tumor microenvironment (TME).
View Article and Find Full Text PDFPPAR Res
December 2024
Department of Laboratory Medicine, The Sixth School of Clinical Medicine, The Affiliated Qingyuan Hospital (Qingyuan People's Hospital), Guangzhou Medical University, Qingyuan, China.
Triple-negative breast cancer (TNBC) is highly heterogeneous and poses a significant medical challenge due to limited treatment options and poor outcomes. Peroxisome proliferator-activated receptors (PPARs) play a crucial role in regulating metabolism and cell fate. While the association between PPAR signal and human cancers has been a topic of concern, its specific relationship with TNBC remains unclear.
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