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Published on: January 3, 2013
PD-1, PD-L1 (B7-H1) and Tumor-Site Immune Modulation Therapy: The Historical Perspective
Jun Wang1, Ruirong Yuan2,3, Wenru Song3
1Yale University School of Medicine, New Haven, CT, 06510, USA.
Abstract:
The current success of targeted inhibition against cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and Programmed Death 1/Programmed Death Ligand 1 (PD-1/PD-L1, herein collectively referred to as PD) pathways is hailed as a cancer immunotherapy breakthrough. PD-L1, known also as B7 homolog 1 (B7-H1), was initially discovered by Dr. Lieping Chen in 1999. To recognize the seminal contributions by Chen to the development of PD-directed therapy against cancer, the Chinese American Hematologist and Oncologist Network (CAHON) decided to honor him with its inaugural Lifetime Achievement Award in Hematology and Oncology at the CAHON's 2015 annual meeting. This essay chronicles the important discoveries made by Chen in the exciting field of immuno-oncology, which goes beyond his original fateful finding. It also argues that PD-directed therapy should be appropriately considered as Tumor-Site Immune Modulation Therapy to distinguish it from CTLA-4-based immune checkpoint blocking agents.
Insights
Targeted inhibition of Programmed Death 1/Programmed Death Ligand 1 (PD-1/PD-L1) pathways represents a cancer immunotherapy breakthrough. This therapy is proposed as Tumor-Site Immune Modulation Therapy, distinct from CTLA-4 blocking agents.
Area of Science:
- Immunology
- Oncology
- Cancer Immunotherapy
Background:
- Targeted inhibition of cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and Programmed Death 1/Programmed Death Ligand 1 (PD-1/PD-L1) pathways has led to significant advancements in cancer immunotherapy.
- Programmed Death Ligand 1 (PD-L1), also known as B7 homolog 1 (B7-H1), was discovered by Dr. Lieping Chen in 1999.
- Dr. Chen's foundational work in immuno-oncology has been recognized with the Chinese American Hematologist and Oncologist Network (CAHON) Lifetime Achievement Award.
Purpose of the Study:
- To honor Dr. Lieping Chen's contributions to PD-directed cancer therapy.
- To review Dr. Chen's key discoveries in immuno-oncology.
- To propose a new classification for PD-directed therapy.
Main Methods:
- Review of seminal discoveries in immuno-oncology.
- Historical account of PD-1/PD-L1 pathway research.
- Conceptual re-framing of PD-directed therapy.
Main Results:
- The success of PD-1/PD-L1 pathway inhibition as a cancer immunotherapy is highlighted.
- Dr. Chen's extensive contributions beyond the initial discovery of PD-L1 are acknowledged.
- A distinction is drawn between PD-directed therapy and CTLA-4-based immune checkpoint inhibitors.
Conclusions:
- PD-1/PD-L1 pathway inhibition is a major breakthrough in cancer immunotherapy.
- PD-directed therapy should be recognized as Tumor-Site Immune Modulation Therapy.
- This classification distinguishes PD-therapy from CTLA-4-based immune checkpoint blocking agents.
