Related Experiment Video

Updated: Oct 4, 2025

Identifying PD-1/PD-L1 Inhibitors with Surface Plasmon Resonance Technology
07:04

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

Published on: May 2, 2025

604

A pan-cancer study of PD-1 and CTLA-4 as therapeutic targets

Zongqiang Cai1, Xiaojie Ang1, Zekun Xu1

  • 1Department of Urology, The First Affiliated Hospital of Soochow University, Suzhou, China.

Translational Cancer Research
|February 4, 2022
PubMed
Abstract

Insights

Programmed death-1 (PD-1) and cytotoxic T lymphocyte-associated protein-4 (CTLA-4) are key immunotherapy targets. This study analyzed their expression and correlation with tumor microenvironment in 33 cancers, revealing prognostic value and potential for immunotherapy patient selection.

Area of Science:

  • Oncology
  • Immunology
  • Genomics

Background:

  • Immunotherapy, utilizing inhibitors of programmed death-1 (PD-1) and cytotoxic T lymphocyte-associated protein-4 (CTLA-4), represents a significant advancement in cancer treatment.
  • Understanding the similarities and differences between PD-1 and CTLA-4 across various cancer types is crucial for optimizing therapeutic strategies.

Purpose of the Study:

  • To investigate the expression patterns of PD-1 and CTLA-4 in 33 distinct cancer types within The Cancer Genome Atlas (TCGA) database.
  • To explore the relationship between PD-1 and CTLA-4 expression, immune microenvironment subtypes, and overall patient survival.
  • To assess the correlation between these immune checkpoint molecules, tumor microenvironment characteristics, and potential drug sensitivity.

Main Methods:

  • Downloaded TNM stage, immune subtype, and tumor microenvironment data for 33 TCGA tumors.
  • Compared PD-1 and CTLA-4 expression in normal versus tumor tissues.
  • Utilized Cox analysis to assess the association between expression and overall survival.
  • Employed ESTIMATE software to evaluate immune cell infiltration and correlate PD-1/CTLA-4 expression with the tumor microenvironment and stemness, alongside gene-drug sensitivity analysis.

Main Results:

  • PD-1 and CTLA-4 exhibited high expression in specific cancers including breast invasive carcinoma (BRCA), cholangiocarcinoma (CHOL), esophageal carcinoma (ESCA), and kidney renal clear cell carcinoma (KIRC).
  • Expression levels were significantly correlated with immune subtypes C2 (IFN-γ-dominant) and C6 (TGF-β-dominant), and positively associated with tumor microenvironmental immune scores.
  • In kidney renal clear cell carcinoma, PD-1 and CTLA-4 expression strongly correlated with advanced clinical stage and a higher microenvironmental score.

Conclusions:

  • PD-1 and CTLA-4 expression are linked to patient prognosis across a majority of tumors studied.
  • These immune checkpoint molecules demonstrate a significant association with the tumor microenvironment.
  • The findings provide valuable insights for identifying patient populations likely to benefit from immunotherapy and guide future research directions.
Keywords:
Programmed death-1 (PD-1)The Cancer Genome Atlas (TCGA)cytotoxic T lymphocyte-associated protein-4 (CTLA-4)pan-cancertumor immunotherapytumor microenvironment

More Related Videos

Multiplexed Immunofluorescence Analysis and Quantification of Intratumoral PD-1+ Tim-3+ CD8+ T Cells09:32

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

Published on: February 8, 2018

14.9K
Monitoring PD-1-Blocking Antibodies Bound to T Cells Derived from a Drop of Peripheral Blood06:07

Monitoring PD-1-Blocking Antibodies Bound to T Cells Derived from a Drop of Peripheral Blood

Published on: February 5, 2020

5.9K

Related Concept Videos

Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...
7.9K
Tumor Immunotherapy01:27

Tumor Immunotherapy

Immunotherapy is a treatment that boosts or manipulates the immune system to fight diseases, including cancer. For instance, by stimulating an immune response through vaccinations against viruses that cause cancers, like hepatitis B virus and human papillomavirus, these diseases can be prevented. Nonetheless, some cancer cells can avoid the immune system due to their rapid mutation and division. The immune response to many cancers involves three phases: elimination, equilibrium, and escape.
711
Combination Therapies and Personalized Medicine02:50

Combination Therapies and Personalized Medicine

Combining two or more treatment methods increases the life span of cancer patients while reducing damage to vital organs or tissue from the overuse of a single treatment. Combination therapy also targets different cancer-inducing pathways, thus reducing the chances of developing resistance to treatment.
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
5.1K