Abstract
Mismatch-repair deficiency in solid tumors predicts their response to PD-1 blockade. Based on this principle, pembrolizumab is approved as standard of care for patients with unresectable or metastatic microsatellite instability–high (MSI-H) cancer. Despite this success, a large majority of metastatic colorectal cancer patients are not MSI-H and do not benefit from checkpoint blockade treatment. Predictive biomarkers to develop personalized medicines and guide clinical trials are needed for these patients. We, therefore, asked whether immunohistologic stratification of metastatic colorectal cancer based on primary tumor PD-L1 expression associated with the presence or absence of extracellular mucin defines a subset of metastatic colorectal cancer patients who exhibit a preexisting antitumor immune response and who could potentially benefit from the checkpoint blockade. To address this, we studied 26 advanced metastatic colorectal cancer patients treated with pembrolizumab (NCT01876511). To stratify patients, incorporation of histopathologic characteristics (percentage of extracellular mucin) and PD-L1 expression at the invasive front were used to generate a composite score, the CPM (composite PD-L1 and mucin) score, which discriminated patients who exhibited clinical benefit (complete, partial, or stable disease) from those patients with progressive disease. When validated in larger cohorts, the CPM score in combination with MSI testing may guide immunotherapy interventions for colorectal cancer patient treatment.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1574-1579 |
| Number of pages | 6 |
| Journal | Cancer Immunology Research |
| Volume | 7 |
| Issue number | 10 |
| DOIs | |
| State | Published - Jan 1 2019 |
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ASJC Scopus subject areas
- Immunology
- Cancer Research
Cite this
Immunopathologic stratification of colorectal cancer for checkpoint blockade immunotherapy. / Llosa, Nicolas J.; Luber, Brandon; Siegel, Nicholas; Awan, Anas H.; Oke, Teniola; Zhu, Qingfeng; Bartlett, Bjarne R.; Aulakh, Laveet K.; Thompson, Elizabeth D.; Jaffee, Elizabeth M.; Durham, Jennifer N.; Sears, Cynthia L.; Le, Dung T.; Diaz, Luis A.; Pardoll, Drew M.; Wang, Hao; Housseau, Franck; Anders, Robert A.
In: Cancer Immunology Research, Vol. 7, No. 10, 01.01.2019, p. 1574-1579.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Immunopathologic stratification of colorectal cancer for checkpoint blockade immunotherapy
AU - Llosa, Nicolas J.
AU - Luber, Brandon
AU - Siegel, Nicholas
AU - Awan, Anas H.
AU - Oke, Teniola
AU - Zhu, Qingfeng
AU - Bartlett, Bjarne R.
AU - Aulakh, Laveet K.
AU - Thompson, Elizabeth D.
AU - Jaffee, Elizabeth M.
AU - Durham, Jennifer N.
AU - Sears, Cynthia L.
AU - Le, Dung T.
AU - Diaz, Luis A.
AU - Pardoll, Drew M.
AU - Wang, Hao
AU - Housseau, Franck
AU - Anders, Robert A.
PY - 2019/1/1
Y1 - 2019/1/1
N2 - Mismatch-repair deficiency in solid tumors predicts their response to PD-1 blockade. Based on this principle, pembrolizumab is approved as standard of care for patients with unresectable or metastatic microsatellite instability–high (MSI-H) cancer. Despite this success, a large majority of metastatic colorectal cancer patients are not MSI-H and do not benefit from checkpoint blockade treatment. Predictive biomarkers to develop personalized medicines and guide clinical trials are needed for these patients. We, therefore, asked whether immunohistologic stratification of metastatic colorectal cancer based on primary tumor PD-L1 expression associated with the presence or absence of extracellular mucin defines a subset of metastatic colorectal cancer patients who exhibit a preexisting antitumor immune response and who could potentially benefit from the checkpoint blockade. To address this, we studied 26 advanced metastatic colorectal cancer patients treated with pembrolizumab (NCT01876511). To stratify patients, incorporation of histopathologic characteristics (percentage of extracellular mucin) and PD-L1 expression at the invasive front were used to generate a composite score, the CPM (composite PD-L1 and mucin) score, which discriminated patients who exhibited clinical benefit (complete, partial, or stable disease) from those patients with progressive disease. When validated in larger cohorts, the CPM score in combination with MSI testing may guide immunotherapy interventions for colorectal cancer patient treatment.
AB - Mismatch-repair deficiency in solid tumors predicts their response to PD-1 blockade. Based on this principle, pembrolizumab is approved as standard of care for patients with unresectable or metastatic microsatellite instability–high (MSI-H) cancer. Despite this success, a large majority of metastatic colorectal cancer patients are not MSI-H and do not benefit from checkpoint blockade treatment. Predictive biomarkers to develop personalized medicines and guide clinical trials are needed for these patients. We, therefore, asked whether immunohistologic stratification of metastatic colorectal cancer based on primary tumor PD-L1 expression associated with the presence or absence of extracellular mucin defines a subset of metastatic colorectal cancer patients who exhibit a preexisting antitumor immune response and who could potentially benefit from the checkpoint blockade. To address this, we studied 26 advanced metastatic colorectal cancer patients treated with pembrolizumab (NCT01876511). To stratify patients, incorporation of histopathologic characteristics (percentage of extracellular mucin) and PD-L1 expression at the invasive front were used to generate a composite score, the CPM (composite PD-L1 and mucin) score, which discriminated patients who exhibited clinical benefit (complete, partial, or stable disease) from those patients with progressive disease. When validated in larger cohorts, the CPM score in combination with MSI testing may guide immunotherapy interventions for colorectal cancer patient treatment.
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UR - http://www.scopus.com/inward/citedby.url?scp=85072848790&partnerID=8YFLogxK
U2 - 10.1158/2326-6066.CIR-18-0927
DO - 10.1158/2326-6066.CIR-18-0927
M3 - Article
C2 - 31439614
AN - SCOPUS:85072848790
VL - 7
SP - 1574
EP - 1579
JO - Cancer immunology research
JF - Cancer immunology research
SN - 2326-6066
IS - 10
ER -