The tumor microenvironment

Plays a key role in tumor progression

 

What is the tumor microenvironment (TME)?

The tumor microenvironment (TME) consists of different cellular, including immune cells, and non-cellular components in and around the tumor. The TME has been recognized to play a significant role in tumor progression.1,2

Why is the TME important? 

The TME shapes tumor evolution (whether the tumor regresses, develops resistance, evades the immune system and/or metastasizes) and consequently impacts patient outcomes.3 An association has been observed between the levels of tumor infiltrating immune cells, key components of the TME, and patient prognosis: a colorectal cancer study showed that higher levels of tumor infiltrating CD3+ immune cells were associated with better disease free survival.4 

What is the role of PD-L1 in the TME? 

Aberrant expression of PD-L1 on tumor cells has been reported to impede anti-tumor immunity, resulting in immune evasion.5 Therefore, interruption of the PD-L1/PD-1 pathway represents an attractive strategy to reinvigorate tumor-specific T cell immunity suppressed by the expression of PD-L1 in the TME. This approach has proven effective: PD-L1 expression on immune cells in the TME has been shown to identify urothelial cancer patients who are most likely to benefit from atezolizumab an anti-PD-L1 drug.6 

References 

  1. NCI Dictionary of Cancer Terms. Tumor microenvironment. http://www.cancer.gov/publications/dictionaries/cancer-terms?cdrid=561725 
  2. AACR. The Function of Tumor Microenvironment in Cancer Progression. http://www.aacr.org/Meetings/Pages/MeetingDetail. aspx?EventItemID=73#.V6pCFPkrKaE 
  3. Chen F, Zhuang X, Lin L, Yu P, Wang Y, Shi Y, Hu G, Sun Y.BMC Med. New horizons in tumor microenvironment biology: challenges and opportunities. 2015 Mar 5;13:45. doi: 10.1186/s12916-015-0278-7. 
  4. Galon J1, Costes A, Sanchez-Cabo F, Kirilovsky A, Mlecnik B, Lagorce-Pagès C, Tosolini M, Camus M, Berger A, Wind P, Zinzindohoué F, Bruneval P, Cugnenc PH, Trajanoski Z, Fridman WH, Pagès F. Type, density, and location of immune cells within human colorectal tumors predict clinical outcome. Science. 2006 Sep 29;313(5795):1960-4. 
  5. Blank, C and Mackensen, A, Contribution of the PD-L1/PD-1 pathway to T-cell exhaustion: an update on implications for chronic infections and tumor evasion. Cancer Immunol Immunother, 2007. 56(5): p. 739-745). 
  6. Ventana Medical Systems Inc. VENTANA PD-L1 (SP142) Assay. Package Insert. http://www.ventana.com/product/1827?type=2357 
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The PD-L1 immunologic checkpoint