Programmed cell death 1 (PD-1) and its ligand (PD-L1) in common cancers and their correlation with molecular cancer type.
Cancer cells expressing PD-1 ligands (PD-L1/PD-L2) inhibit immune-modulatory T-cell activation facilitating disease progression. Preliminary clinical trials exploring interruption of PD-1/PD-L1 signaling showed benefit in several cancer types. We analyzed the distribution of PD-1-positive tumor-infiltrating lymphocytes (TIL) and cancer cells' expression of PD-L1 in a molecularly profiled cohort of 437 malignancies (380 carcinomas, 33 sarcomas, and 24 melanomas). We showed that the presence of PD-1(+) TILs significantly varied among cancer types (from 0% in extraskeletal myxoid chondrosarcomas to 93% in ovarian cancer), and was generally associated with the increased number of mutations in tumor cells (P = 0.029). Cancer cell expression of PD-L1 varied from absent (in Merkel cell carcinomas) to 100% (in chondro- and liposarcomas), but showed the inverse association with the number of detected mutations (P = 0.004). Both PD-1 and PD-L1 expression were significantly higher in triple-negative breast cancers (TNBC) than in non-TNBC (P < 0.001 and 0.017, respectively). Similarly, MSI-H colon cancers had higher PD-1 and PD-L1 expression than the microsatellite stable tumors (P = 0.002 and 0.02, respectively). TP53-mutated breast cancers had significantly higher PD-1 positivity than those harboring other driver mutations (e.g., PIK3CA; P = 0.002). In non-small cell lung cancer, PD-1/PD-L1 coexpression was identified in 8 cases (19%), which lacked any other targetable alterations (e.g., EGFR, ALK, or ROS1). Our study demonstrated the utility of exploring the expression of two potentially targetable immune checkpoint proteins (PD-1/PD-L1) in a substantial proportion of solid tumors, including some aggressive subtypes that lack other targeted treatment modalities.
Caris Life Sciences, Phoenix, Arizona. zgatalica@carisls.com.
Zoran
Z
Gatalica
Department of Preventive Medicine and Public Health, Creighton University, Omaha, Nebraska.
Carrie
C
Snyder
Caris Life Sciences, Phoenix, Arizona.
Todd
T
Maney
Caris Life Sciences, Phoenix, Arizona.
Anatole
A
Ghazalpour
Caris Life Sciences, Phoenix, Arizona.
Daniel A
DA
Holterman
Caris Life Sciences, Phoenix, Arizona.
Nianqing
N
Xiao
Caris Life Sciences, Phoenix, Arizona.
Peggy
P
Overberg
Caris Life Sciences, Phoenix, Arizona.
Inga
I
Rose
Caris Life Sciences, Phoenix, Arizona.
Gargi D
GD
Basu
Department of Pathology, Clinical Center, University of Sarajevo, Sarajevo, Bosnia and Herzegovina.
Semir
S
Vranic
Department of Preventive Medicine and Public Health, Creighton University, Omaha, Nebraska.
Henry T
HT
Lynch
Translational Genomic Research Institute and Virginia G. Piper Cancer Center, Phoenix, Arizona.
Daniel D
DD
Von Hoff
The Angeles Clinic and Research Institute, Los Angeles, California.
Omid
O
Hamid
D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D009369:Neoplasms / Q000235:genetics*; D011379:Prognosis; D061026:Programmed Cell Death 1 Receptor / Q000037:antagonists & inhibitors*
D061026:Programmed Cell Death 1 Receptor