The Role of Oncogenes and Redox Signaling in the Regulation of PD-L1 in Cancer

Christophe Glorieux1, Xiaojun Xia1, Peng Huang1

  • 1State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou 510060, China.

Cancers
|September 10, 2021
PubMed

Insights

Tumor cells evade immune surveillance by upregulating programmed cell death ligand 1 (PD-L1). This review details how oncogenic signals, growth factor receptors, and redox signaling control PD-L1 expression, impacting cancer immunotherapy response.

Area of Science:

  • Oncology
  • Immunology
  • Molecular Biology

Background:

  • Tumor cells exploit immune checkpoints, like PD-L1/PD-1 signaling, to evade immune surveillance.
  • High PD-L1 expression in cancer is linked to immune evasion and therapeutic response.
  • Understanding PD-L1 regulation is crucial for effective cancer immunotherapy.

Purpose of the Study:

  • To review mechanisms regulating PD-L1 expression in cancer.
  • To explore the roles of oncogenic signals, growth factor receptors, and redox signaling in PD-L1 regulation.
  • To discuss the clinical relevance and therapeutic strategies targeting PD-L1.

Main Methods:

  • Literature review of mechanisms controlling PD-L1 expression.
  • Focus on oncogenic signals (c-Myc, EML4-ALK, K-ras, p53 mutants).
  • Analysis of growth factor receptors (EGFR, FGFR) and redox signaling pathways.

Main Results:

  • Oncogenic signals, growth factor receptors, and redox signaling are key regulators of PD-L1.
  • These pathways exhibit distinct and cooperative mechanisms to control PD-L1 expression.
  • PD-L1 regulation impacts tumor immune evasion and response to immunotherapy.

Conclusions:

  • Targeting PD-L1 regulatory mechanisms offers therapeutic potential.
  • Combination therapies may enhance treatment efficacy by modulating PD-L1.
  • Further research into PD-L1 regulation is vital for advancing cancer immunotherapy.

Related Concept Videos

Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
6.7K
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...
4.7K
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...
3.9K
Cancer-Critical Genes I: Proto-oncogenes01:33

Cancer-Critical Genes I: Proto-oncogenes

Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
9.3K
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...
7.1K
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a...
4.2K