Markers for response to immunotherapy: Increased eosinophils = good. Increased Myeloid Suppressor cells = not so good.

Myeloid Cells and related chronic inflammatory factors as novel predictive markers in melanoma treatment with ipilimumab.  Gebhardt, Sevko, Jiang, et al.  Clin Cancer Res. 2015 Aug 19.

Ipi improves survival of patients with metastatic melanoma.  Since only about 20% of patients experience long-term benefit, reliable markers are needed to predict response.  Analysis of blood of 59 Stage IV melanoma patients was analyzed before treatments and at different times during treatment.  An early increase in eosinophil count during treatment with ipi was associated with an improved clinical response. In contrast, elevated numbers of monocytic myeloid-derived suppressor cells (moMDSCs), neutrophils, and monocytes were found in non-responders (n=36) as compared to levels in responding patients (n=23).  Non-responders also produced more nitric oxide and granulocytic MDSCs expressed higher levels of PD-L1 ... suggesting their enhanced immunosuppressive capacity.  Upon the first ipi infusion, non-responders displayed high serum concentrations of S100A8/A9 and HMGB1 that attract and activate MDSCs.

So....folks with increased eosinophils do better.  Folks with increased numbers of myeloid-derived suppressor cells, neutrophils, and monocytes do not.  Here is more data to support the same findings:

Lab values that may predict response to Ipi

Eosinophilia and a positive response to nivo and pembro

In this link Weber talks ipi and combo's, several immunotherapy combo's are discussed...but the relevant part addresses the blood work from the folks taking nivo in my study:
 

Looking at pretreatment parameters in the periphery and the tumor-
Only baseline MDSC, myeloid derived suppressor cells, proved to be significant.
These are CD14, HLA-DR low, CD11 B+ cells, classic myeloid derived suppressor cells which express high levels of PDL1 and other check point proteins.
Neutrophil derived MDSC cells were not related.
The more myeloid suppressor cells you have, the worse the patient did both in response rate and survival. 
Weber hopes to soon have results of the levels of MDSC from within the tumors of these patients and see how that level related to outcomes.
You can block MDSC by incubating it with PD1 antibody as well as other check point proteins, so he is writing a grant proposal currently to test a combo of nivo with MDSC depletion.
Measurements of the T-regs in the periphery - Levels decreased in responders, in non-responders it went up. For this reason, also thinks that nivo with T-reg depletion is worth investigation.


Here, in a synopsis of articles about the positive effects of combining immunotherapy and radiation, Radiation for melanoma, better when combined with immunotheapy!, once again....patients do better when MDSCs are few and far between:  Concomitant with tumor regression from radiation, they noted that radiation and anti-PD-L1 worked together to reduce the local accumulation of tumor-inflitrating myeloid-derived suppressor cells (MDSCs)... {Note:  Remember, these are the bad guys that block your T cells.  In my study, the folks with high levels of MDSCs did least well, while those with the lowest levels did better.  That's why, some researchers, like Weber, are talking about depleting these cells in patients FIRST...then administering anti-PD1 or other immunotherapies!!}  So...the data acquired in this study demonstrated evidence of the interaction between radiation and T cells....and a basis for the rational design of combination therapy with immune modulators and radiotherapy.

Really thinking the idea about depleting MDSCs at the start may really be the way to go here!!!  Best - c