Background: Tumor-infiltrating T lymphocytes (TIL) play an important role in primary colorectal cancer, but their activity in liver metastases has not yet been investigated. The aim of this study was to examine whether tumor-selective infiltration, activation, and cytotoxic activity of TIL can be demonstrated in situ in colorectal liver metastases.
Methods: TIL were obtained from liver metastases and corresponding normal liver tissue of 16 patients with colorectal liver metastases. Characterization of TIL in situ was performed by multicolor flowcytometric analysis. Presence of tumor antigen-reactive T cells was evaluated by interferon gamma Elispot analysis.
Results: TIL in colorectal liver metastases responding against tumor antigens were present in most patients. Although the proportions of CD3(+) T cells were comparable in liver metastasis and normal liver tissue, metastases contained significantly enhanced proportions of CD4(+) cells (49% vs. 22%, P < .001). Among all CD4(+) T helper cells, the proportion of activated (CD4(+)CD25(+)) effector cells was significantly increased in liver metastases (15.0% vs. 7.8%, P = .003). Metastases showed significantly higher proportions of activated (CD69(+) [70.1% vs. 49.8%, P = .02] and CD25(+) [4.1% vs. .6%, P = .06]) and cytotoxically active (CD107a(+)) CD8(+) TIL (3.2% vs. 1.3%, P = .03). Importantly, the presence of activated T helper cells correlated with the frequencies of cytotoxic T lymphocytes that exerted cytotoxic activity in situ (P = .02).
Conclusion: CD4(+) and CD8(+) TIL are selectively activated in liver metastases, and cytotoxic T lymphocytes exert tumor-selective cytotoxic activity in situ in the presence of activated T helper cells, suggesting the requirement of in-situ-activated T helper cells for efficient cytotoxic T lymphocytes effector function.
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http://dx.doi.org/10.1245/s10434-008-9971-5 | DOI Listing |
J Clin Med
January 2025
Department of Pharmacology, Faculty of Medicine, Wrocław Medical University, 50-345 Wrocław, Poland.
: Medullary carcinoma of the small intestine is an exceptionally rare subtype of gastrointestinal cancer, characterized by its solid growth pattern and lack of glandular structures, which complicate timely diagnosis. During the COVID-19 pandemic, diagnostic delays for rare cancers became increasingly common due to the prioritization of COVID-related cases and patient reluctance to seek medical attention. : We present the case of a 70-year-old male initially misdiagnosed with COVID-19, whose persistent symptoms led to the eventual discovery of medullary carcinoma.
View Article and Find Full Text PDFInt J Mol Sci
January 2025
Department of Medical Biophysics, Institute of Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, 90-236 Lodz, Poland.
Hepatocellular carcinoma (HCC) cells critically depend on PARP1 and CHK1 activation for survival. Combining the PARP inhibitor (PARPi) olaparib with a CHK1 inhibitor (MK-8776, CHK1i) produced a synergistic effect, reducing cell viability and inducing marked oxidative stress and DNA damage, particularly in the HepG2 cells. This dual treatment significantly increased apoptosis markers, including γH2AX and caspase-3/7 activity.
View Article and Find Full Text PDFMedicina (Kaunas)
January 2025
Department of Medical Oncology, Faculty of Medicine, Medeniyet University, Prof. Dr. Süleyman Yalçın City Hospital, Istanbul 34700, Turkey.
: Early-onset breast cancer (EOBC), particularly in patients under 40, presents with distinct biological characteristics and worse survival outcomes compared to late-onset cases. Despite intensive treatments, EOBC patients, especially those with hormone receptor-positive, HER2-negative (HR+/HER2-) subtypes, show poorer prognosis. CDK4/6 inhibitors, combined with endocrine therapy (ET) have become the standard for HR+/HER2- metastatic breast cancer, yet younger patients are underrepresented in clinical trials.
View Article and Find Full Text PDFCancers (Basel)
January 2025
Department of Interventional Oncology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China.
Objective: To determine the impact of trans-arterial embolization (TAE) on overall survival (OS) in patients with liver metastases from gastroenteropancreatic neuroendocrine tumors (LM-GEP-NETs) and to identify factors that may influence tumor response to TAE treatment.
Methods: This study included patients with histologically and radiologically confirmed LM-GEP-NETs who received TAE treatment at The First Affiliated Hospital, Sun Yat-sen University, between November 2016 and January 2023. Imaging responses were assessed using Response Evaluation Criteria in Solid Tumors (RECIST) 1.
Cancers (Basel)
January 2025
Department of Radiotherapy, Research Centre for Digital Medicine, VUB-UZ Brussel, 1090 Brussels, Belgium.
: Inadequate dosing and respiratory motion contribute to local recurrence for oligometastatic disease (OMD). While short-term LC rates are well-documented, data on long-term LC remain limited. This study investigated long-term LC after stereotactic body radiotherapy (SBRT), using respiratory motion management techniques.
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