Background: The effectiveness of immune checkpoint inhibitors in treating gallbladder cancer (GBC) remains unsatisfactory. Recently, several new immune checkpoints have been identified. However, investigations exploring these immune checkpoints in GBC are limited. In this study, we aim to investigate the expression patterns and clinical implications of various immune checkpoints, and further characterize the spatial and quantitative heterogeneity of immune components in GBC.
Methods: We employed single and multiplex immunohistochemistry to evaluate the expression of five immune checkpoint markers and four immune cell markers in the primary tumor core, hepatic invasion margin, and liver metastasis. Subsequently, we analyzed their interrelationships and their prognostic significance.
Results: We observed a robust positive correlation between PD1/TIM3 expression in GBC (R = 0.614, P < 0.001). The co-expression of PD1/TIM3 exhibited a synergistic effect in predicting poor prognosis among postoperative GBC patients. Further analysis revealed that the prognostic significance of PD1/TIM3 was prominent in the subgroup with high infiltration of CD8 + T cells (P < 0.001). Multiplex immunohistochemistry reveals that PD1 + TIM3 + FOXP3 + cells constitute a significant proportion of FOXP3 + TILs in GBC tissue. Moreover, the co-high expression of PD1 and TIM3 is positively correlated with the accumulation of CD8 + TILs at the hepatic invasion margin. Lastly, our findings indicated reduced expression levels of immune checkpoints and diminished immune cell infiltration in liver metastases compared to primary tumors.
Conclusions: Increased co-expression of PD1/TIM3 is associated with poor prognosis in GBC patients and is related to the heterogeneity of immune microenvironment between GBC primary tumor and its hepatic invasion margin or liver metastases, which may be a potential target for future immunotherapy of GBC.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10571407 | PMC |
| http://dx.doi.org/10.1186/s12967-023-04589-3 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Adding checkpoint inhibitors to first-line chemotherapy for NUT carcinoma patients.
NPJ Precis Oncol
January 2025
Department of Medicine III, LMU University Hospital, Munich, Germany.
Rare cancers present significant challenges in diagnosis, treatment, and research, accounting for up to 25% of global cancer cases. Due to their rarity and atypical presentations, they are often misdiagnosed, resulting in late-stage detection and poor outcomes. Here, we describe a patient case with advanced metastatic nasopharynx NUT carcinoma, one of the rarest and most aggressive cancers.
View Article and Find Full Text PDFFinding a needle in a haystack: functional screening for novel targets in cancer immunology and immunotherapies.
Oncogene
January 2025
Department of Obstetrics and Gynecology, Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE, West China Second Hospital, State Key Laboratory of Biotherapy, and Department of Neurosurgery, West China Hospital, Sichuan University and Collaborative Innovation Center, Chengdu, P. R. China.
Genome-wide functional genetic screening has been widely used in the biomedicine field, which makes it possible to find a needle in a haystack at the genetic level. In cancer research, gene mutations are closely related to tumor development, metastasis, and recurrence, and the use of state-of-the-art powerful screening technologies, such as clustered regularly interspaced short palindromic repeat (CRISPR), to search for the most critical genes or coding products provides us with a new possibility to further refine the cancer mapping and provide new possibilities for the treatment of cancer patients. The use of CRISPR screening for the most critical genes or coding products has further refined the cancer atlas and provided new possibilities for the treatment of cancer patients.
View Article and Find Full Text PDFPrognostic factors and outcomes of adjuvant and first-line metastatic treatments in melanoma a Turkish oncology group study.
Sci Rep
January 2025
Division of Medical Oncology, Marmara University School of Medicine, Istanbul, Turkey.
Management of melanoma has changed significantly with the discovery of targeted therapies and immune checkpoint inhibitors (ICI). Our aim in the study is to determine which treatment alternatives, specifically dabrafenib plus trametinib and ICIs, are effective in adjuvant therapy and which treatment is effective as first-line metastatic therapy. This retrospective, multicenter study included 120 patients diagnosed with stage IIIB-IIID melanoma receiving both adjuvant and first-line metastatic treatment between 2007 and 2023.
View Article and Find Full Text PDFA mouse model to assess immunotherapy-related colitis.
Methods Cell Biol
January 2025
Laboratory of Translational Oncology, Program in Solid Tumors, Cima Universidad de Navarra, Cancer Center Clínica Universidad de Navarra (CCUN), Pamplona, Spain; Department of Biochemistry and Genetics, School of Sciences, Universidad de Navarra, Pamplona, Spain; Navarra's Health Research Institute (IDISNA), Pamplona, Spain; Centro de Investigación Biomédica en Red Cáncer (CIBERONC), Madrid, Spain. Electronic address:
Combined blockade of the immune checkpoints PD-1 and CTLA-4 has shown remarkable efficacy in patients with melanoma, renal cell carcinoma, non-small-cell lung cancer and mesothelioma, among other tumor types. However, a proportion of patients suffer from serious immune-related adverse events (irAEs). In severe cases, a reduction of the doses or the complete cessation of the treatment is required, limiting the antitumor efficacy of these treatments.
View Article and Find Full Text PDFUrine proteomics defines an immune checkpoint-associated nephritis signature.
J Immunother Cancer
January 2025
Section of Nephrology, Division of Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
Immune checkpoint inhibitor (ICI) therapy is a cornerstone treatment for many cancers, but it can induce severe immunotoxicity, including acute interstitial nephritis (AIN). Currently, kidney biopsy is required to differentiate ICI-AIN from other causes of acute kidney injury (AKI). However, this invasive approach can lead to morbidity, delayed glucocorticoid treatment for patients with AIN, and unnecessarily prolonged suspension of ICI therapy in non-AIN patients.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!