Cancer cell-intrinsic PD-1: Its role in malignant progression and immunotherapy

Area of Science:

• Oncology
• Immunology
• Molecular Biology

Background:

• Programmed cell death protein-1 (PD-1), or CD279, is a key immune checkpoint receptor expressed on immune cells.
• PD-1 binds to PD-L1/PD-L2 on tumor cells, facilitating immune evasion and is a target for cancer immunotherapy.
• Recent studies reveal PD-1's intrinsic variant (iPD-1) expressed within cancer cells, suggesting novel roles in tumorigenesis.

Purpose of the Study:

• To review the multifaceted role of intrinsic PD-1 (iPD-1) in cancer cell tumorigenesis and progression.
• To elucidate the molecular mechanisms underlying iPD-1's contrasting functions in different cancer types.
• To discuss the implications of iPD-1 for optimizing anti-PD-1/PD-L1 immunotherapy and combination strategies.

Main Methods:

• Literature review and synthesis of existing research on PD-1 and iPD-1.
• Analysis of studies investigating iPD-1 expression and function across various cancer types.
• Discussion of clinical data and therapeutic strategies involving PD-1 inhibitors.

Main Results:

• iPD-1 exhibits context-dependent roles, suppressing tumorigenesis in non-small cell lung cancer and colon cancer.
• Conversely, iPD-1 promotes tumorigenesis in melanoma, hepatocellular carcinoma, pancreatic ductal adenocarcinoma, thyroid cancer, glioblastoma, and triple-negative breast cancer.
• iPD-1's distinct functions may explain variable responses to anti-PD-1 therapies.

Conclusions:

• Intrinsic PD-1 (iPD-1) represents a critical factor in cancer development with opposing effects depending on the tumor type.
• Understanding iPD-1 mechanisms is essential for predicting and enhancing the efficacy of current immunotherapies.
• Targeting or considering iPD-1's role could lead to improved combination therapies for diverse cancers.