1. Converting Cold into Hot Tumors by Combining Immunotherapies
John B.A.G. Haanen 
Cell 
Volume 170, Issue 6, Pages (September 2017)
DOI: /j.cell
Copyright © 2017 Elsevier Inc. Terms and Conditions

2. Figure 1
Schematic Course of Events following Oncolytic Virus and Anti-PD-1 Treatment in Metastatic Melanoma
(A) Patient with advanced-stage melanoma receiving combination therapy consisting of anti-PD-1 intravenously plus intralesional injection of talimogene laherparepvec.
(B) Close up of tumor microenvironment prior to injection with HSV virus: melanoma cells in vascular stroma lacking immune infiltrate (“cold” tumor).
(C) Close up of tumor microenvironment shortly after administration of the viral vaccine. Infected tumor cells are killed by the virus; the virus spreads to other tumor cells. Innate immune cells are attracted by local inflammation through (among others) type I IFN release, and dendritic cells (DCs) are attracted and matured by local secretion of GM-CSF. DCs take up dying tumor cells and present tumor antigens in the draining lymph node area to tumor-specific T cells. T cells are activated, proliferate, and home to the tumor site that is injected and to distant non-injected metastases.
(D) Close up of tumor microenvironment with now-dense T cell infiltrate (“hot” tumor). Activated T cells are PD-1 positive, and upon targeting tumor cells, released IFN-γ induces expression of PD-L1 on tumor cells, which leads to shut down of T cell immune response. The systemically delivered anti-PD-1 blocks the PD-1/PD-L1 interaction and reactivates the suppressed T cells, leading to tumor cell killing.
Cell  , DOI: ( /j.cell )
Copyright © 2017 Elsevier Inc. Terms and Conditions