What Is PTI?
Normal inflammation vs Pro-Tumor Inflammation (PTI)
Inflammation is the immune system’s normal response to infections and disease3-5:
- When not properly regulated, inflammation can become unhealthy6
- For more than 150 years, scientists have been exploring the link between unregulated inflammation and cancer. PTI has been recognized as one of the hallmarks of cancer7,8
- There is preliminary evidence that PTI is associated with non-small cell lung cancer (NSCLC)9
Through inflammatory mediators, PTI is believed to help1,2:
Facilitate oncogenic processes, promoting tumor cell proliferation and cancer progression
Suppress the immune response against a tumor by altering the tumor microenvironment
Multiple cell types and cytokines are implicated in PTI and function as inflammatory mediators in the tumor microenvironment. These include macrophages, interleukins, and tumor necrosis factor–alpha (TNF-α).1
Overview of the tumor microenvironment10-12
As a tumor grows it develops its own ecosystem, known as the tumor microenvironment. Among other functions, the tumor microenvironment helps the tumor survive by shielding it from the immune system, in part through the recruitment of immunosuppressive cells such as regulatory T cells (Tregs), macrophages, and myeloid-derived suppressor cells (MDSCs) that suppress cytotoxic T cells.
Role of IL-1β
Interleukin-1 beta (IL-1β) plays a key role in PTI13
There is preliminary evidence that IL-1β helps facilitate PTI by activating tumor processes and recruiting immunosuppressive cells.14-16
IL-1β signaling contributes to tumor growth and progression through activation of numerous transcription factors, including nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB).15,17
IL-1β contributes to suppression of the immune response against the tumor by recruiting immunosuppressive cells to the tumor microenvironment. Infiltrating MDSCs, Tregs, and tumor-associated macrophages (TAMs) contribute to the deactivation of cytotoxic T cells in the tumor microenvironment.16,18
Preclinical data support that IL-1β, a key cytokine in the tumor microenvironment, is one of the drivers of PTI required for tumor growth, survival, and metastasis.9,15
Multiple other cell types and cytokines are also implicated, such as macrophages, interleukins, and TNF-α.1
According to preliminary evidence, IL-1β expression can be elevated in NSCLC and may correlate with poor prognosis19-21
One of the Hallmarks of Cancer
For more than 150 years, scientists have been exploring the link between unregulated inflammation and cancer. PTI has been recognized as one of the hallmarks of cancer7,8
Adapted with permission from Hanahan D et al, 2011.
Novartis is proud to be the leader in PTI research
We are exploring the role of PTI in lung cancer.9,13 The need for bold and transformative research could not be more urgent. At Novartis, we will relentlessly continue to pursue this research.
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