Next Article in Journal
Polymorphisms within Immune Regulatory Pathways Predict Cetuximab Efficacy and Survival in Metastatic Colorectal Cancer Patients
Previous Article in Journal
Predictive Markers for Malignant Urothelial Transformation in Balkan Endemic Nephropathy: A Case–Control Study
Open AccessArticle

Divergent Resistance Mechanisms to Immunotherapy Explain Responses in Different Skin Cancers

by Emmanuel Dollinger 1,2,3,4,†, Daniel Bergman 1,†, Peijie Zhou 1, Scott X. Atwood 2,3,4,5,* and Qing Nie 1,2,3,4,*
1
Department of Mathematics, University of California, Irvine, CA 92697, USA
2
Department of Developmental and Cell Biology, University of California, Irvine, CA 92697, USA
3
NSF-Simons Center for Multiscale Cell Fate Research, University of California, Irvine, CA 92697, USA
4
Center for Complex Biological Systems, University of California, Irvine, CA 92697, USA
5
Chao Family Comprehensive Cancer Center, University of California, Irvine, CA 92697, USA
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Cancers 2020, 12(10), 2946; https://doi.org/10.3390/cancers12102946
Received: 28 August 2020 / Revised: 28 September 2020 / Accepted: 9 October 2020 / Published: 13 October 2020
(This article belongs to the Special Issue Molecular Mechanisms of Skin Cancer)
Despite the successes of immune checkpoint therapy in treating metastatic skin cancers, most patients either fail to respond or become unresponsive to immunotherapy. We found that the cell–cell communication of two different immune cell types, macrophages and memory B cells, correlate very strongly with the response to immunotherapy. We built a mathematical model based on these results that predict different skin cancers would have different response rates and predict that a high ratio of memory B cells to macrophages is optimal for a response to immunotherapy.
The advent of immune checkpoint therapy for metastatic skin cancer has greatly improved patient survival. However, most skin cancer patients are refractory to checkpoint therapy, and furthermore, the intra-immune cell signaling driving response to checkpoint therapy remains uncharacterized. When comparing the immune transcriptome in the tumor microenvironment of melanoma and basal cell carcinoma (BCC), we found that the presence of memory B cells and macrophages negatively correlate in both cancers when stratifying patients by their response, with memory B cells more present in responders. Moreover, inhibitory immune signaling mostly decreases in melanoma responders and increases in BCC responders. We further explored the relationships between macrophages, B cells and response to checkpoint therapy by developing a stochastic differential equation model which qualitatively agrees with the data analysis. Our model predicts BCC to be more refractory to checkpoint therapy than melanoma and predicts the best qualitative ratio of memory B cells and macrophages for successful treatment. View Full-Text
Keywords: immunotherapy; single-cell transcriptomics; biomarkers; cell–cell communication; mathematical oncology immunotherapy; single-cell transcriptomics; biomarkers; cell–cell communication; mathematical oncology
Show Figures

Figure 1

MDPI and ACS Style

Dollinger, E.; Bergman, D.; Zhou, P.; Atwood, S.X.; Nie, Q. Divergent Resistance Mechanisms to Immunotherapy Explain Responses in Different Skin Cancers. Cancers 2020, 12, 2946.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Search more from Scilit
 
Search
Back to TopTop