Study Examines Association of PD-1 and PD-L1 Expression in Primary and Metastatic Renal Cell Carcinomas

Cleveland Clinic researcher and oncologist Brian Rini, MD, presented a poster on renal cell cancer at the American Society of Clinical Oncology’s 2015 Genitourinary Cancers Symposium in Orlando, Fla. The presentation was titled “Association of PD-1 and PD-L1 protein expression in matched primary and metastatic renal cell carcinoma tumors.”

The presentation showcased the methodology and results of a retrospective study conducted by Cleveland Clinic researchers. The study’s goal was to determine the association of PD-1 expression on the surface of tumor cells.

Background

Therapy targeting programmed death (PD)-1 and PD-L1 proteins has activity in metastatic renal cell carcinoma (mRCC). Expression of these proteins on tumor and infiltrating immune cells is associated with a higher response to drugs inhibiting this pathway. However, these associations have been made based on primary tumor expression, while therapy is directed against metastatic deposits.

“There are a lot of potential new therapies directed at this pathway, so we were hoping to gain early insight into what will be a practical clinical question of whether or not expression of certain proteins is associated with benefit to this new therapy, and if different organs vary in their protein expression.,” says Dr. Rini.

Study Methods

Patients with clear cell mRCC and metastases who had undergone resection of both the primary and at least one metastatic tumor were included. “Cleveland Clinic has a large bank of kidney tumors with the matching metastatic site that we were able to use for testing,” Dr. Rini says.

Samples were evaluated for PD-1 and PD-L1 expression by immunohistochemistry using anti-PD-1 clone NAT105 and Merck proprietary anti-PD-L1 clone 22C3. Stained sections were scored for PD-1 and PD-L1 using a semi-quantitative 0 to 5 scale (0 = negative, 1 = rare, 2 = low, 3 = moderate, 4 = high, 5 = very high). PD-1 expression was limited to cells with lymphoid morphology; PD-L1 expression was evaluated for both tumor and non-tumor (inflammatory, endothelial) cells. Linear regression analysis was performed to assess significance of correlations.

Study Results

Fifty matched primary and metastatic RCC tissue sets were analyzed with 48 evaluable matched pairs. “In the tumors we studied, the level of expression was similar in the primary kidney tumors and the metastatic sites,” Dr. Rini says.

PD-1 score greater than 3 (considered positive) was detected in nine primary and nine metastatic sites (18 percent). PD-L1 score greater than 3 was detected in nine primary tumors (18 percent) and 12 metastatic sites (24 percent). There was a correlation between PD-1 scores for primary and metastatic pairs and between PD-L1 scores for primary and metastatic pairs. There was also an association between PD-1 score and PD-L1 score for primary tumors and for metastatic sites.

Future Research

The study concluded that, in general, the expression of PD-1 and PD-L1 in a primary clear-cell RCC tumor is associated with metastatic site expression, although there is a substantial percentage of patients with discordance.

“The drugs that are aimed at this pathway are still investigational and we’re still in preliminary studies, so the results are not yet clinically impactable,” says Dr. Rini. “We need to look at a lot more samples, and then we can begin to apply the data to clinical practice.”

Disclosures

The pharmaceutical company Merck analyzed the assays for this study. Dr. Rini has done consulting and clinical research with Merck in the past.