98%
921
2 minutes
20
Background/aim: Immunoscore (IS) is an important evaluation method for the tumor immune microenvironment (TIME); however, formal IS analysis requires designated reagents and a specific digital pathology software and image data analysis. This study aimed to investigate whether simplified IS (s-IS) can substitute formal IS upon modifying the location of the assessment of the numbers of immune cells and verify that the addition of T cell subset markers to s-IS can enhance the prognostic impact in patients with colorectal cancer (CRC).
Patients And Methods: A total of 82 CRC cases were included in this study. Immunohistochemical analysis was performed using CD3/CD8/CD45RO/FOXP3 on tissue specimens; the expression levels were calculated in the center and perimeter of the tumors using digital pathology. The clinical prognostic significance of the expression of these markers was investigated by concordance index comparison according to their location of assessment and combinations.
Results: In the univariate analysis, the CD3, CD8, and FOXP3 levels were significant prognostic factors. Moreover, for each T cell subset marker, the assessment of each T cell subset marker at the tumor perimeter had a stronger prognostic power than that in the tumor center. The modified s-IS (s-IS plus FOXP3 evaluation) was an independent prognostic factor for recurrence-free survival and overall survival through multivariate analysis and demonstrated the best prognostic power compared to other T subset marker combinations.
Conclusion: In CRC, TIME evaluation could be simplified by assessing CD3- and CD8-positive T cells in the perimeter of the tumor, and additional FOXP3 evaluation would empower the ability of s-IS evaluation in prognostic assessment.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.21873/anticanres.16565 | DOI Listing |
Sci Adv
September 2025
Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
(phosphatidylserine synthase 1) encodes an enzyme that facilitates production of phosphatidylserine (PS), which mediates a global immunosuppressive signal. Here, based on in vivo CRISPR screen, we identified PTDSS1 as a target to improve anti-PD-1 therapy. Depletion of in tumor cells increased expression of interferon-γ (IFN-γ)-regulated genes, including , , , and , even in the absence of IFN-γ stimulation in vitro.
View Article and Find Full Text PDFSci Transl Med
September 2025
Key Laboratory of Breast Cancer in Shanghai, Department of Breast Surgery, Precision Cancer Medicine Center, Fudan University Shanghai Cancer Center, Shanghai 200032, P. R. China.
Triple-negative breast cancers (TNBCs) lack predictive biomarkers to guide immunotherapy, especially during early-stage disease. To address this issue, we used single-cell RNA sequencing, bulk transcriptomics, and pathology assays on samples from 171 patients with early-stage TNBC receiving chemotherapy with or without immunotherapy. Our investigation identified an enriched subset of interferon (IFN)-induced CD8 T cells in early TNBC samples, which predict immunotherapy nonresponsiveness.
View Article and Find Full Text PDFPLoS Pathog
September 2025
Centre for Virus Research, The Westmead Institute for Medical Research, Westmead, Australia.
Dendritic cells (DCs) are potent antigen-presenting cells and play a key role in facilitating the sexual transmission of HIV, functioning as a delivery system responsible for trafficking the virus from exposed barrier sites to their key target cells, CD4 T cells. Although the role of DCs in HIV transmission is well established, the recent advent of high-parameter, single-cell detection technologies, coupled with improved cell isolation techniques, has led to the rapid reclassification of the DC landscape, particularly within human barrier tissues. The identification of new subsets introduces the challenge of incorporating previously understood transmission principles with new, cell-specific, functional nuances to identify the key DCs responsible for facilitating HIV infection.
View Article and Find Full Text PDFCancer Res
September 2025
The Wistar Institute, Philadelphia, PA, United States.
Parkin is a mitochondria-associated E3 ubiquitin (Ub) ligase that mediates mitophagy and organelle quality control. More recently, Parkin has been implicated in stimulating antitumor immunity and reprogramming the tumor immune microenvironment. Here, we showed that Parkin ubiquitinates the alarmin molecule, high mobility group box-1 (HMGB1) on Lys146 (K146) using predominantly K48 linkages.
View Article and Find Full Text PDFAnticancer Drugs
September 2025
Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College.
Nonsmall cell lung cancer (NSCLC) with SMARCA4 deficiency represents a rare subset of lung tumors characterized by early metastasis, poor response to chemotherapy, and unfavorable prognosis. Established therapy strategies for SMARCA4-deficient NSCLC remain elusive. While immune checkpoint inhibitors have been proposed as a potential solution, their efficacy remains uncertain.
View Article and Find Full Text PDF