| Title |
Immunological Correlates of Response to Immune Checkpoint Inhibitors in Metastatic Urothelial Carcinoma
|
|---|---|
| Published in |
Targeted Oncology, September 2018
|
| DOI | 10.1007/s11523-018-0595-9 |
| Pubmed ID | |
| Authors |
Alice Tzeng, C. Marcela Diaz-Montero, Patricia A. Rayman, Jin S. Kim, Paul G. Pavicic, James H. Finke, Pedro C. Barata, Marcelo Lamenza, Sarah Devonshire, Kim Schach, Hamid Emamekhoo, Marc S. Ernstoff, Christopher J. Hoimes, Brian I. Rini, Jorge A. Garcia, Timothy D. Gilligan, Moshe C. Ornstein, Petros Grivas |
| Abstract |
The identification of prognostic and/or predictive biomarkers for response to immune checkpoint inhibitors (ICI) could help guide treatment decisions. We assessed changes in programmed cell death-1 (PD1)/PD1 ligand (PDL1) expression in key immunomodulatory cell subsets (myeloid-derived suppressor cells [MDSC]; cytotoxic T lymphocytes [CTL]) following ICI therapy and investigated whether these changes correlated with outcomes in patients with metastatic urothelial carcinoma (mUC). Serial peripheral blood samples were collected from ICI-treated mUC patients. Flow cytometry was used to quantify PD1/PDL1 expression on MDSC (CD33+HLADR-) and CTL (CD8+CD4-) from peripheral blood mononuclear cells. MDSC were grouped into monocytic (M)-MDSC (CD14+CD15-), polymorphonuclear (PMN)-MDSC (CD14-CD15+), and immature (I)-MDSC (CD14-CD15-). Mixed-model regression and Wilcoxon signed-rank or rank-sum tests were performed to assess post-ICI changes in immune biomarker expression and identify correlations between PD1/PDL1 expression and objective response to ICI. Of 41 ICI-treated patients, 26 received anti-PDL1 (23 atezolizumab/3 avelumab) and 15 received anti-PD1 (pembrolizumab) therapy. Based on available data, 27.5% had prior intravesical Bacillus Calmette-Guérin therapy, 42% had prior neoadjuvant chemotherapy, and 70% had prior cystectomy or nephroureterectomy. Successive doses of anti-PDL1 correlated with decreased percentage of PDL1+ (%PDL1+) M-MDSC, while doses of anti-PD1 correlated with decreased %PD1+ M- and I-MDSC. Although pre-treatment %PD1+ CTL did not predict response, a greater %PD1+ CTL within 9 weeks after ICI initiation correlated with objective response. Treatment with ICI correlated with distinct changes in PD1/PDL1-expressing peripheral immune cell subsets, which may predict objective response to ICI. Further studies are required to validate immune molecular expression as a prognostic and/or predictive biomarker for long-term outcomes in mUC. |
X Demographics
The data shown below were collected from the profiles of 3 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Italy | 1 | 33% |
| United States | 1 | 33% |
| Unknown | 1 | 33% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 2 | 67% |
| Science communicators (journalists, bloggers, editors) | 1 | 33% |
Mendeley readers
The data shown below were compiled from readership statistics for 33 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 33 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 6 | 18% |
| Student > Doctoral Student | 3 | 9% |
| Student > Bachelor | 3 | 9% |
| Student > Master | 3 | 9% |
| Professor | 2 | 6% |
| Other | 7 | 21% |
| Unknown | 9 | 27% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 10 | 30% |
| Biochemistry, Genetics and Molecular Biology | 6 | 18% |
| Agricultural and Biological Sciences | 3 | 9% |
| Immunology and Microbiology | 2 | 6% |
| Social Sciences | 1 | 3% |
| Other | 1 | 3% |
| Unknown | 10 | 30% |
Attention Score in Context
This research output has an Altmetric Attention Score of 2. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 01 October 2018.
All research outputs
#13,937,707
of 23,105,443 outputs
Outputs from Targeted Oncology
#201
of 556 outputs
Outputs of similar age
#179,259
of 341,609 outputs
Outputs of similar age from Targeted Oncology
#4
of 14 outputs
Altmetric has tracked 23,105,443 research outputs across all sources so far. This one is in the 38th percentile – i.e., 38% of other outputs scored the same or lower than it.
So far Altmetric has tracked 556 research outputs from this source. They receive a mean Attention Score of 2.8. This one has gotten more attention than average, scoring higher than 63% of its peers.
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We're also able to compare this research output to 14 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 71% of its contemporaries.