Stenzl - Figure 42

Association Between Molecular Subtype and Immune Infiltration/Suppression

FIG. 42:  Where is the future research headed, at least in the differentiation of tumors  and personalization of treatment?  There is an association between molecular subtype and the degree of immune infiltration and suppression in tumors (Figure) that suggests there are other mechanisms than the new antigen burden that can drive the development of immune infiltrated tumors.[28]  We have to look at certain substances that block EMT activity or decrease NF-kappaB (NF-κB) activity in tumors, and thus may be beneficial for the activity of, for example, checkpoint inhibitors.  Lowering certain enzymes such as those activated by peroxisome proliferator-activated receptor-gamma (PPAR-γ) may be detrimental for the patient by making the immune environment so poor that none of the checkpoint inhibitors currently available can work in these patients. 

With the development of new substances for systemic therapy of urothelial cancer it will also be necessary to improve the possibility of subtyping both the tissue and DNA uptake in the plasma in order to show the response rate, as well as the time these inhibitors need to respond, in order to pinpoint an effective therapy for advanced urothelial cancer.  Much work remains to be done, but this is a very exciting time, when not only new substances, but also their individual use and individual response rates are being studied.  This means that we can be expecting good results and benefit for the patients with metastatic or advanced urothelial cancer – patients have been a little “orphaned” in the last few years.

References

[28]

Kardos J, Chai S, Mose LE, et al. Claudin-low bladder tumors are immune infiltrated and actively immune suppressed. JCI Insight. 2016;1:e85902  https://doi.org/10.1172/jci.insight.85902