Circulating tumor cell assay to non-invasively evaluate PD-L1 and other therapeutic targets in multiple cancers

Abstract

Biomarker directed selection of targeted anti-neoplastic agents such as immune checkpoint inhibitors, small molecule inhibitors and monoclonal antibodies form an important aspect of cancer treatment. Immunohistochemistry (IHC) analysis of the tumor tissue is the method of choice to evaluate the presence of these biomarkers. However, a significant barrier to biomarker testing on tissue is the availability of an adequate amount of tissue and need for repetitive sampling due to tumor evolution. Also, tumor tissue testing is not immune to inter- and intra-tumor heterogeneity. We describe the analytical and clinical validation of a Circulating Tumor Cell (CTC) assay to accurately assess the presence of PD-L1 22C3 and PD-L1 28.8, ER, PR and HER2, from patients with solid tumors to guide the choice of suitable targeted therapies. Analytically, the test has high sensitivity, specificity, linearity and precision. Based on a blinded case control study, the clinical sensitivity and specificity for PD-L1 (22C3 and 28.8) was determined to be 90% and 100% respectively. The clinical sensitivity and specificity was 83% and 89% for ER; 80% and 94% for PR; 63% and 89% for HER2 (by ICC); and 100% and 92% for HER2 (by FISH), respectively. The performance characteristics of the test support its suitability and adaptability for routine clinical use.

Investigating Radiotherapy Effects on PD-L1 Expression in Circulating Tumor Cells: An Exploratory Study

“…As liquid biopsy, CTC offers a promising approach to discovering predictive biomarkers for patient selection in immunotherapy [7]. This method overcomes challenges linked to repeated tissue sampling, often complicated by limited tissue samples and tumor evolution [8].…”

Evaluation of premetastatic changes in lymph nodes(pN0) of oral tongue tumour: A prospective observational Study

“… 58 The expression of PD-L1 on circulating tumor cells may also be a reliable predictive biomarker. 60 …”

“…58 The expression of PD-L1 on circulating tumor cells may also be a reliable predictive biomarker. 60 PD -L 1 expression in conventional immunohistochemistry assays lacks accuracy and reliability as the staining of cytoplasmic proteins interferes with cell membrane protein estimation. 61 As discussed earlier, STAT3 activation increases immunosuppression and found to induce immunosuppression by upregulating PD-L1 in head and neck squamous cell carcinoma.…”