Tumor cells inhibit the activation of ILC2s through up-regulating PD-1 expression

Chaoyun Yin1,2, Yani Pa2, Guangyu Li2

  • 1Department of Emergency Medicine, The Affiliated Jiangyin Hospital of Nantong University, Jiangyin, P. R. China.

Abstract

Insights

Programmed cell death-1 (PD-1) up-regulation inhibits innate lymphoid cells (ILC2s) in lung cancer. Blocking PD-1 with anti-PD-1 therapy restores ILC2 function and suppresses tumor growth, offering a new immunotherapy strategy.

Area of Science:

  • Immunology
  • Oncology
  • Cell Biology

Background:

  • Programmed cell death-1 (PD-1) and programmed cell death ligand-1 (PD-L1) interactions on immune cells can hinder anti-tumor responses.
  • Understanding these interactions is crucial for improving cancer immunotherapy efficacy.

Purpose of the Study:

  • To investigate the role of PD-1 expression in lung cancer-infiltrating type II innate lymphoid cells (ILC2s).
  • To explore the potential of targeting the PD-1/PD-L1 axis for enhancing ILC2-based cancer immunotherapy.

Main Methods:

  • Analysis of PD-1 expression in lung cancer-infiltrating ILC2s.
  • In vitro co-culture experiments with tumor cells and anti-PD-1 treatment.
  • In vivo studies using LLC-bearing nude mice treated with anti-PD-1.

Main Results:

  • PD-1 was highly up-regulated on lung cancer-infiltrating ILC2s, suppressing their activation and function.
  • Anti-PD-1 treatment restored ILC2 cytokine secretion and anti-tumor activity in vitro.
  • In vivo anti-PD-1 therapy promoted ILC2 activation and inhibited tumor growth.

Conclusions:

  • A novel PD-1/PD-L1 regulatory mechanism involving innate immune cells was identified.
  • Targeting this axis offers a promising strategy for ILC2-based immunotherapy in cancer treatment.

Related Concept Videos

Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
4.5K
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.
520
T Cell Types and Functions01:24

T Cell Types and Functions

When T cells with CD4 markers are activated, they give rise to two types of effector cells: helper T cells and regulatory T cells. Meanwhile, T cells with CD8 markers differentiate into effector cytotoxic T cells. The differentiation of CD4 T cells into helper T cell subsets, such as Th1, Th2, and Th17 cells, is dependent on the antigen type, antigen-presenting cell, and regulatory cytokines.
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
1.0K
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
4.7K
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
6.5K
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
3.8K