Intratumor heterogeneity of PD-L1 expression in head and neck squamous cell carcinoma

Abstract

Intratumor heterogeneity may contribute to the ambiguous clinical results on PD-L1 status as a predictor for immunotherapy response in patients with HNSCC. This decreases the utility of PD-L1 expression from single tumour biopsies as a predictive biomarker. In this prospective study, intratumor heterogeneity of PD-L1 expression in HNSCC was investigated with both Tumour Proportion Score (TPS) and Combined Positive Score (CPS). Thirty-three whole surgical specimens from 28 patients with HNSCC were included. PD-L1 expression in six random core biopsies from each surgical specimen was used to assess the concordance between multiple biopsies and the negative predictive value of a single negative core biopsy. With 1% cut off, 36% of the specimens were concordant with TPS and 52% with CPS. With a 50% cut-off value the concordance was 70% with TPS and 55% with CPS. Defining a tumour as positive if just a single-one of the biopsies was positive, the negative predictive value (NPV) of a single negative core biopsy was 38.9 and 0% (1% cut off), and 79.9% and 62.8% (50% cut off) for TPS and CPS, respectively. In conclusion, PD-L1 positivity varies markedly within the tumour, both with TPS and CPS, challenging the utility of this biomarker.

Prognostic Impact of PD-L1 Expression in Malignant Salivary Gland Tumors as Assessed by Established Scoring Criteria: Tumor Proportion Score (TPS), Combined Positivity Score (CPS), and Immune Cell (IC) Infiltrate

“…The comparability between the results is limited [14,15]. Due to the reported heterogeneity of PD-L1 expression in other head and neck malignancies [23], we also see the use of tissue microarray (TMA) slides for the first assessment of PD-L1 expression somewhat critical. Our result of high PD-L1 expression in AC, NOS is in line with data from Mukaigawa et al who reported PD-L1 expression (1% cutoff, clone E1L3N) in 36% of AC, NOS but only in rare cases of AdCC (2%), MEC (9%), and ACC (0%) [22].…”

Tumor control via targeting PD-L1 with chimeric antigen receptor modified NK cells

“…This suggests that PD-L1 CAR haNK monotherapy may be most effective in patients harboring PD-L1+ tumors with evidence of genomic alterations or expression defects predicted to lead to insensitivity to T cell detection or elimination. Greater than 80% of patients with HNSCC have a combined positive score of >1 indicative of PD-L1 positivity(28), but significant heterogeneity of PD-L1 expression exists within individual tumors(29). PD-L1-dependent and independent mechanisms of killing by PD-L1 CAR haNKs are likely to be required for maximum treatment efficacy.…”

Current Understanding of the Mechanisms Underlying Immune Evasion From PD-1/PD-L1 Immune Checkpoint Blockade in Head and Neck Cancer

“…The caveat of using CPS at the 1% cutoff to select HNSCC patients for PD-1 ICB is that intratumor heterogeineity should be considered. Rasmussen et al have prospectively investigated the intratumor heterogeneity in PD-L1 expression in HNSCC in 28 patients with a total of 33 whole surgical specimens (98). With 1% cut off, 52% of the six random core biopsies from each surgical specimen was concordant with CPS.…”

“…With 1% cut off, 52% of the six random core biopsies from each surgical specimen was concordant with CPS. Defining a tumor as positive if just a single-one of the core biopsies was positive using CPS at 1% cut-off, the negative predictive value of a single negative core biopsy was 0% (98).…”