The prognostic value of programmed death-ligand 1 (PD-L1) expression in resected colorectal cancer without neoadjuvant therapy - differences between antibody clones and cell types.

BACKGROUND: Programmed death-ligand 1 (PD-L1) expression on tumor cells is associated with poor prognosis in several malignancies, while partly contradictory and inconclusive results have been presented for colorectal cancer (CRC). This study aimed to evaluate PD-L1 as a prognostic biomarker in CRC by comparing three different antibody clones. METHODS: Patients surgically treated for CRC between January 1st, 2007, and December 31st, 2015, in Kalmar County, Sweden, were retrospectively included. Tissue microarrays from 862 primary tumors without neoadjuvant treatment were assessed for immunohistochemical expression of PD-L1 in tumor cells (TC) and immune cells (IC) using clones 73-10, SP263, and 22C3. Cox regression proportional hazard models were used to estimate hazard ratios for overall survival (OS) and disease-free interval (DFI) in univariable and multivariable analyses, with 1% and 5% set as cut-offs for positive expression in TC and IC respectively. RESULTS: PD-L1 expression in TC was found in 89 (10%) cases for clone 73-10, 76 (9%) for clone SP263, and 38 (4%) for clone 22C3, while the numbers for IC were 317 (37%) cases for clone 73-10, 264 (31%) for clone SP263, and 89 (10%) for clone 22C3. PD-L1 expression in IC was associated with prolonged OS and DFI in univariable analysis for all three clones. The link to prolonged DFI remained in multivariable analysis for 73-10 and SP263, but only for 73-10 regarding OS. PD-L1 expression in TC was not prognostic of OS in any analysis, while it was associated with prolonged DFI for SP263, and a trend was seen for 73-10. The link to prolonged DFI remained for SP263 and was strengthened for 73-10 in multivariable analysis. CONCLUSIONS: The prognostic value of PD-L1 expression in both IC and TC differs between antibody clones, with 73-10 and SP263 being more reliable for prognostic information than 22C3 in resected CRC.

PD-L1 Expression and Clinicopathological Factors in Renal Cell Carcinoma: A Comparison of Antibody Clone 73-10 With Clone 28-8.

BACKGROUND/AIM: Expression of programmed death ligand-1 (PD-L1) is associated with poor prognosis in renal cell carcinoma (RCC). Although a new antibody clone for immunohistochemical assay, 73-10, has shown greater sensitivity than other assays (28-8, 22C3, SP142, and SP263) in non-small cell lung cancer, PD-L1 expression using 73-10 has never been assessed in RCC. Therefore, this study aimed to evaluate the association of clinicopathological factors with PD-L1 expression detected by clone 73-10 and compare it with that detected by 28-8. PATIENTS AND METHODS: Tissue microarray samples from 582 patients who underwent radical or partial nephrectomy for RCC were immunohistochemically assessed using clones 73-10 and 28-8. RESULTS: The positivity for PD-L1 expression in RCC by 73-10 was higher than that of 28-8 and significantly associated with worse pathological factors and a higher risk of cancer-specific mortality. CONCLUSION: Positivity for PD-L1 expression by 73-10, as compared to 28-8, was associated with worse clinicopathological factors and prognosis for patients with RCC.

PD-L1 expression as a predictive biomarker for immune checkpoint inhibitors: between a dream and a nightmare.

PD-L1 is an important predictive biomarker for treatment by immune checkpoint inhibitors (ICIs). ICIs are now indicated for the treatment of various cancer depending on the level of expression of PD-L1 on tumor cells. PD-L1 testing is done using immunohistochemistry with five different assays approved as companion diagnostic for ICIs. However, these assays have different score reporting methods and do not accurately measure PD-L1 expression. Exosomal PD-L1 testing has recently emerged as an alternative for cell-surface PD-L1 testing however studies are still premature and more extensive knowledge about this new potential biomarker is needed.

Lay abstract Immunotherapy is a new strategy for cancer treatment that aims to reactivate the body's own immune system, originally disabled by the tumor, to fight the malignancy. Immune checkpoint inhibitors are compounds developed for this purpose. However, their efficacy is subject to the abundance of their target, PD-L1, on the surface of cancer cells. Conventional PD-L1 testing through tumor biopsy has multiple technical drawbacks. Another form of PD-L1 secreted by the tumor into the circulation has emerged as a potential target for assessing immune checkpoint inhibitors efficacy but studies are still in their preliminary stages and further testing is required.