Patterns and prognostic relevance of PD-1 and PD-L1 expression in colorectal carcinoma.

Mod Pathol 2016 11 22;29(11):1433-1442. Epub 2016 Jul 22.

Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

Immune checkpoint blockade targeting the programmed death-1 (PD-1) pathway has shown efficacy in several types of cancers including mismatch-repair-deficient colorectal carcinoma. In some tumor types, programmed death-ligand 1 (PD-L1) expression detected by immunohistochemistry has shown utility as a predictive marker for response to anti-PD-1 therapies. This utility, however, remains to be determined in colorectal carcinoma. In addition, although tumor-infiltrating lymphocytes have been associated with better prognosis in colorectal carcinoma, the prognostic value of PD-1 expression in these lymphocytes and its interaction with PD-L1 expression still await investigation. To address these questions, we performed a pilot study to evaluate the patterns of PD-L1 and PD-1 immunohistochemical expression on colorectal carcinoma cells and their tumor-infiltrating lymphocytes, respectively. Using tissue microarray, we found that 5% (19/394) of colorectal carcinomas exhibited high tumor PD-L1 expression, and 19% (76/392) had elevated numbers of PD-1-positive tumor-infiltrating lymphocytes. PD-L1 levels correlated with PD-1 levels (P<0.001), and mismatch-repair-deficient tumors had significantly higher rates of high PD-L1 and PD-1 expression when compared with mismatch-repair-proficient tumors (18% vs 2% and 50% vs 13%, respectively; P<0.001 for both). Staining intensity was also stronger for both markers in mismatch-repair-deficient tumors. Furthermore, we observed that among patients with mismatch-repair-deficient colorectal carcinoma, PD-1/PD-L1 expression stratified recurrence-free survival in an inter-dependent manner: an association between high PD-1-positive tumor-infiltrating lymphocytes and improved recurrence-free survival (P=0.041) was maintained only when the tumors had low-level PD-L1 expression (P=0.006); patients whose tumors had both high PD-1-positive tumor-infiltrating lymphocytes and high PD-L1 expression had a significantly worse recurrence-free survival (P<0.001). Thus, our results not only provide a foundation for further assessment of PD-L1 immunohistochemistry as a predictive marker for anti-PD-1 therapy in colorectal carcinoma, they also shed light on the prognostic impact of tumor-infiltrating lymphocytes in different subsets of mismatch-repair-deficient colorectal carcinomas.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5083129PMC
http://dx.doi.org/10.1038/modpathol.2016.139DOI Listing
November 2016
35 Reads

Publication Analysis

Top Keywords

colorectal carcinoma
28
pd-l1 expression
24
tumor-infiltrating lymphocytes
24
mismatch-repair-deficient colorectal
12
recurrence-free survival
12
pd-1-positive tumor-infiltrating
12
expression
10
pd-l1
10
colorectal
9
high pd-1-positive
8
pd-1 expression
8
colorectal carcinomas
8
predictive marker
8
expression colorectal
8
mismatch-repair-deficient tumors
8
high pd-l1
8
pd-l1 pd-1
8
lymphocytes
7
carcinoma
7
tumor-infiltrating
6

References

(Supplied by CrossRef)

O Hamid et al.
N Engl J Med 2013

RS Herbst et al.
Nature 2014

T Powles et al.
Nature 2014

SL Topalian et al.
N Engl J Med 2012

JR Brahmer et al.
N Engl J Med 2012

SL Topalian et al.
J Clin Oncol 2014

J Sunshine et al.
Curr Opin Pharmacol 2015

JM Taube et al.
Clin Cancer Res 2014

JR Brahmer et al.
J Clin Oncol 2010

DT Le et al.
N Engl J Med 2015

A Mantovani et al.
Lancet 2008

Similar Publications