Long ago (2016) I wrote a post about Biomarkers - blood components, circulating tumor cells AND of the tumor itself which included this:
"Then, there's the examination of the properties of the tumor sample itself. This article talks about looking at the tumor in regard to how well it is being recognized by the immune system....specifically t-cells:
In other words - according to that study, MHC-II positivity in your tumor is good if you want to gain a response from anti-PD-1.
Back in 2014 I wrote: SRS combined with anti-PD1 makes things better in ratties....this one's for you Artie!!!! Where, in an article discussing how combining radiation with immunotherapy can improve responses in melanoma patients, there was this:
"These immune-stimulating effects of radiotherapy were significantly increased when combined with either anti-PD-1 or regulatory T cell (Treg) depletion, resulting in improved local tumor control. ...radiotherapy increased the percentage of antigen-experienced T-cells and effector memory T-cells. ...radiotherapy up-regulates tumor associated antigen-MHC complexes, enhances antigen cross-presentation in the draining lymph node, and increased T-cell infiltration into tumors."
This month, there is a new report (with lots of melanoma big dogs as authors) on how MHC proteins affect response to anti-CTLA4 and anti-PD-1. Here's the link if you want to read it yourself! http://stm.sciencemag.org
MHC proteins confer differential sensitivity to CTLA-4 and PD-1 blockade in untreated metastatic melanoma Rodig, Gusenleitner, Jackson,..., Weber, Wolchok, Postoww, Pavlick, Chesney, Hodi. Science Translational Medicine, July 2018.
MHC-ing immunotherapy response ~ Currently, there is no way to predict response to anti–CTLA-4 cancer immunotherapy. Using data from two published independent phase 2 clinical trials, Rodig et al. showed that MHC class I expression in advanced melanoma predicted resistance to anti–CTLA-4, but not anti-PD-1, treatment, which may need MHC class II to be effective. These results may explain why patients on combined therapy do better on average, with one drug overcoming the limitations of the other. The combination is also more toxic than single agents; knowing which drug to administer to which patients could make melanoma immunotherapy less taxing without sacrificing efficacy.
So across all these studies, the basic results seem consistent. If your tumors have high expression of MHC class I proteins, you are more likely to need to take CTLA-4 (ipi/Yervoy) in order to gain a response because you are less likely to benefit from anti-PD-1. On the other hand, if your tumors are high in the expression of MHC class II proteins, you are more likely to be able to gain a good response to anti-PD-1 (nivo/Opdivo or pembro/Keytruda) alone and don't need to risk the side effects from ipi!!
Clear as mud??? While no one thing is an end all/be all in melanoma world, this is ONE MORE simple test that we should start utilizing in order to help melanoma patients find the treatment option that would be best for them!!! Just say'n!!! - c