Divergent Resistance Mechanisms to Immunotherapy Explain Responses in Different Skin Cancers
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 com...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2020-10-01
|
| Series: | Cancers |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2072-6694/12/10/2946 |
| _version_ | 1797551201380728832 |
|---|---|
| author | Emmanuel Dollinger Daniel Bergman Peijie Zhou Scott X. Atwood Qing Nie |
| author_facet | Emmanuel Dollinger Daniel Bergman Peijie Zhou Scott X. Atwood Qing Nie |
| author_sort | Emmanuel Dollinger |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T15:41:12Z |
| format | Article |
| id | doaj.art-29dadb2aa8254902a7f9f70062ddcc33 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T15:41:12Z |
| publishDate | 2020-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-29dadb2aa8254902a7f9f70062ddcc332023-11-20T16:48:33ZengMDPI AGCancers2072-66942020-10-011210294610.3390/cancers12102946Divergent Resistance Mechanisms to Immunotherapy Explain Responses in Different Skin CancersEmmanuel Dollinger0Daniel Bergman1Peijie Zhou2Scott X. Atwood3Qing Nie4Department of Mathematics, University of California, Irvine, CA 92697, USADepartment of Mathematics, University of California, Irvine, CA 92697, USADepartment of Mathematics, University of California, Irvine, CA 92697, USADepartment of Developmental and Cell Biology, University of California, Irvine, CA 92697, USADepartment of Mathematics, University of California, Irvine, CA 92697, USAThe 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.https://www.mdpi.com/2072-6694/12/10/2946immunotherapysingle-cell transcriptomicsbiomarkerscell–cell communicationmathematical oncology |
| spellingShingle | Emmanuel Dollinger Daniel Bergman Peijie Zhou Scott X. Atwood Qing Nie Divergent Resistance Mechanisms to Immunotherapy Explain Responses in Different Skin Cancers Cancers immunotherapy single-cell transcriptomics biomarkers cell–cell communication mathematical oncology |
| title | Divergent Resistance Mechanisms to Immunotherapy Explain Responses in Different Skin Cancers |
| title_full | Divergent Resistance Mechanisms to Immunotherapy Explain Responses in Different Skin Cancers |
| title_fullStr | Divergent Resistance Mechanisms to Immunotherapy Explain Responses in Different Skin Cancers |
| title_full_unstemmed | Divergent Resistance Mechanisms to Immunotherapy Explain Responses in Different Skin Cancers |
| title_short | Divergent Resistance Mechanisms to Immunotherapy Explain Responses in Different Skin Cancers |
| title_sort | divergent resistance mechanisms to immunotherapy explain responses in different skin cancers |
| topic | immunotherapy single-cell transcriptomics biomarkers cell–cell communication mathematical oncology |
| url | https://www.mdpi.com/2072-6694/12/10/2946 |
| work_keys_str_mv | AT emmanueldollinger divergentresistancemechanismstoimmunotherapyexplainresponsesindifferentskincancers AT danielbergman divergentresistancemechanismstoimmunotherapyexplainresponsesindifferentskincancers AT peijiezhou divergentresistancemechanismstoimmunotherapyexplainresponsesindifferentskincancers AT scottxatwood divergentresistancemechanismstoimmunotherapyexplainresponsesindifferentskincancers AT qingnie divergentresistancemechanismstoimmunotherapyexplainresponsesindifferentskincancers |