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Published on: August 21, 2013
Programmed cell death protein 1 in cancer cells
Chunlian Wei1,2, Meijun Liu3,2, Weifen Zhang4,5
1School of Basic Medical Sciences, Shandong Second Medical University, Weifang, 261053, Shandong, PR China.
Abstract:
Programmed cell death protein 1 (PD-1) is frequently detected in certain subsets of tumor cells, and our understanding of PD-1 signaling consequences has expanded to include control of tumor growth, stemness and drug resistance. Nonetheless, tumor cell-intrinsic PD-1 has been comparatively underexplored in relation to PD-1 expressed on the surface of immune cells as an immune checkpoint, despite the imperative need to comprehensively elucidate the underlying mechanisms of action for achieving optimal responses in tumor immunotherapy. Here, we review the roles of the regulation and function of tumor-intrinsic PD-1 from its expression to degradation processes. Our primary focus is on unraveling its enigmatic influence on tumorigenesis and progression as proposed by recent findings, while navigating the labyrinthine network of regulatory mechanisms governing its expression and intricate functional interplay. We also discuss how the elucidation of the mechanistic underpinnings of tumor-intrinsic PD-1 expression holds the potential to explain the divergent therapeutic outcomes observed with anti-PD-1-based combination therapies, thereby furnishing indispensable insights crucial for synergistic anti-tumor strategies.
Insights
Tumor cell-intrinsic Programmed cell death protein 1 (PD-1) plays a key role in tumor growth and drug resistance. Understanding its regulation and function is crucial for improving anti-PD-1 cancer immunotherapy outcomes.
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- Programmed cell death protein 1 (PD-1) is recognized for its immune checkpoint function on immune cells.
- PD-1 expression within tumor cells influences tumor growth, stemness, and drug resistance.
- The role of tumor-intrinsic PD-1 remains less understood compared to its immune cell counterpart.
Purpose of the Study:
- To review the regulation and function of tumor-intrinsic PD-1.
- To elucidate the mechanisms underlying PD-1 expression and function within tumor cells.
- To explore the implications of tumor-intrinsic PD-1 for anti-PD-1 combination therapies.
Main Methods:
- Literature review focusing on recent findings regarding tumor-intrinsic PD-1.
- Analysis of regulatory mechanisms governing PD-1 expression and degradation in tumor cells.
- Synthesis of information on the functional interplay of tumor-intrinsic PD-1 in tumorigenesis.
Main Results:
- Tumor-intrinsic PD-1 significantly impacts tumor progression and development.
- Recent findings highlight complex regulatory networks controlling tumor cell PD-1 expression.
- Elucidating these mechanisms may explain varied responses to anti-PD-1 therapies.
Conclusions:
- Tumor-intrinsic PD-1 is a critical factor in cancer, beyond its immune checkpoint role.
- Further research into tumor cell PD-1 regulation is essential for optimizing cancer immunotherapy.
- Understanding tumor-intrinsic PD-1 offers new avenues for synergistic anti-tumor strategies.
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