Related Experiment Video

Updated: Jan 24, 2026

Multiplexed Immunofluorescence Analysis and Quantification of Intratumoral PD-1+ Tim-3+ CD8+ T Cells
09:32

Multiplexed Immunofluorescence Analysis and Quantification of Intratumoral PD-1+ Tim-3+ CD8+ T Cells

Published on: February 8, 2018

15.4K

Expression of PD-1 and CTLA-4 Are Negative Prognostic Markers in Renal Cell Carcinoma

Andreas Kahlmeyer1, Christine G Stöhr2, Arndt Hartmann3

  • 1Department of Urology and Pediatric Urology, University Hospital Erlangen, Friedrich Alexander-University Erlangen-Nuernberg, 91054 Erlangen, Germany. andreas.kahlmeyer@uk-erlangen.de.

Journal of Clinical Medicine
|May 30, 2019
PubMed

Insights

Checkpoint inhibition (CI) therapy is standard for metastatic renal cell carcinoma (RCC). However, PD-1 and CTLA-4 expression in tumor-infiltrating mononuclear cells (TIMC) are linked to worse survival, with CTLA-4 independently predicting poor outcomes.

Area of Science:

  • Oncology
  • Immunology
  • Pathology

Background:

  • Immuno-oncological therapy with checkpoint inhibition (CI) is a standard treatment for metastatic renal cell carcinoma (RCC).
  • The prognostic significance of CI target molecule expression in RCC remains controversial.
  • Understanding these markers can refine patient risk stratification and treatment strategies.

Purpose of the Study:

  • To investigate the prognostic value of programmed cell death protein 1 (PD-1), programmed death-ligand 1 (PD-L1), and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) expression in RCC.
  • To determine if these markers predict cancer-specific survival (CSS) and overall survival (OS) in patients not treated with CI therapy.
  • To identify potential biomarkers for high-risk RCC patients.

Main Methods:

  • Analysis of 342 unselected RCC tumor samples using immunohistochemistry (IHC).
  • Quantification of PD-1, PD-L1, and CTLA-4 expression in tumor cells and tumor-infiltrating mononuclear cells (TIMC).
  • Survival analysis (log-rank, univariate and multivariate Cox regression) for CSS and OS in patients without prior CI exposure.

Main Results:

  • PD-1 expression in TIMC was found in 9.4% and CTLA-4 expression in TIMC in 6.3% of samples.
  • Both PD-1 and CTLA-4 expression in TIMC were significantly associated with worse OS and CSS.
  • CTLA-4 expression was an independent prognostic marker for worse OS and CSS in multivariate analysis.
  • Combined PD-1 and CTLA-4 expression identified patients at the highest risk for poor outcomes.

Conclusions:

  • PD-1 and CTLA-4 expression in TIMC are associated with unfavorable survival in RCC patients.
  • CTLA-4 expression serves as an independent prognostic marker in RCC.
  • The combined assessment of PD-1 and CTLA-4 expression in TIMC may help identify high-risk RCC patients, guiding future therapeutic decisions.
Keywords:
CTLA-4PD-1PD-L1immunohistochemistrymortalitiyprognostic markerrenal cell carcinoma

More Related Videos

Y-90 Radioembolization and PD-1 Inhibitor as Neoadjuvant Treatment in Hepatocellular Carcinoma09:11

Y-90 Radioembolization and PD-1 Inhibitor as Neoadjuvant Treatment in Hepatocellular Carcinoma

Published on: May 24, 2024

1.1K
Identifying PD-1/PD-L1 Inhibitors with Surface Plasmon Resonance Technology07:04

Identifying PD-1/PD-L1 Inhibitors with Surface Plasmon Resonance Technology

Published on: May 2, 2025

1.1K

Related Concept Videos

PD Controller: Design01:26

PD Controller: Design

In automotive engineering, car suspension systems often employ Proportional Derivative (PD) controllers to enhance performance. PD controllers are utilized to adjust the damping force in response to road conditions. A controller, acting as an amplifier with a constant gain, demonstrates proportional control, with output directly mirroring input.
Designing a continuous-data controller requires selecting and linking components like adders and integrators, which are fundamental in Proportional,...
636
Cell Specific Gene Expression01:58

Cell Specific Gene Expression

Multicellular organisms contain a variety of structurally and functionally distinct cell types, but the DNA in all the cells originated from the same parent cells. The differences in the cells can be attributed to the differential gene expression. Liver cells, whose functions include detoxification of blood, production of bile to metabolize fats, and synthesis of proteins essential for metabolism, must express a specific set of genes to perform their functions. Gene expression also varies with...
16.3K
Negative Regulator Molecules01:23

Negative Regulator Molecules

Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
38.3K
Time-Domain Interpretation of PD Control01:07

Time-Domain Interpretation of PD Control

Proportional-Derivative (PD) control is a widely used control method in various engineering systems to enhance stability and performance. In a system with only proportional control, common issues include high maximum overshoot and oscillation, observed in both the error signal and its rate of change. This behavior can be divided into three distinct phases: initial overshoot, subsequent undershoot, and gradual stabilization.
Consider the example of control of motor torque. Initially, a positive...
388
Positive, Negative, and Zero Work00:58

Positive, Negative, and Zero Work

Work is done on an object when energy is transferred to the object. In other words, work is done when a force acts on a body that undergoes a displacement from one position to another. By definition, the work done by a force is the integral of the force with respect to the displacement along its path. Forces can vary as a function of position, and displacements can occur along various paths between two points. The magnitude of a force multiplied by the cosine of the angle that the force makes...
22.1K
Chromatin Position Affects Gene Expression02:35

Chromatin Position Affects Gene Expression

Chromatin is the massive complex of DNA and proteins packaged inside the nucleus. The complexity of chromatin folding and how it is packaged inside the nucleus greatly influences  access to genetic information. Generally, the nucleus' periphery is considered transcriptionally repressive, while the cell's interior is considered a transcriptionally active area. 
Topologically Associated Domains (TADs)
The 3-dimensional positioning of chromatin in the nucleus influences the...
24.7K