175P - Differential impact of increased neoantigen load on PD-L1 positive immune cell infiltrations in comparison to PD-L1 expression on tumor cells

Background

Programmed Death-Ligand 1 (PD-L1) expression is a crucial biomarker for immunotherapy in cancer treatment. This study analyses the distribution of PD-L1 (Dako 22C3, 28-8 and Ventana SP142) across various solid tumors to understand the prevalence of PD-L1 across solid tumors and impact of TMB and MSI.

Methods

A total of 2334 solid tumor samples were evaluated for PD-L1 expression using the 22C3 (2312 cases) and 28-8 (1780 cases), SP142 (177 cases) assays. Histopathological classification, age, and gender data were recorded. TMB, MSI data were available for a subset of the samples, their correlations with PD-L1 was analysed.

Results

PD-L1 positivity (TPS or CPS or IC ≥1) was seen in 709/2334 (30%) of all samples. Highest incidence of PD-L1 positivity was seen in Head and neck (63%), Bladder (57%) and Lung (42%) cancers and lowest in CNS (14%), Sarcomas (13%), GIT (10%). At this cut off, the PD-L1 positivity was not significantly different based on MSI status (31% MSI-H vs 28% in MSS) or TMB status (35% in TMB-High vs 29% in TMB Low). Similarly, no difference was observed in median TPS score across TMB or MSI status. However, the median CPS values for both 22C3 and 28-8 were significantly higher in MSI High (Median 22C3 CPS 20 and Median 28-8 CPS 16) vs MSS (Median 22C3 and 28-8 CPS <1). Such significant difference wasn’t observed based on High TMB (Median 22C3 and 28-8 CPS 3) against low TMB (Median 22C3 and 28-8 CPS <1). Table: 175P

Positivity for cancer specific PD-L1 thresholds

Conclusions

Higher CPS scores and not TPS scores, in MSI-H tumors compared to MSS tumors show the increased neoantigen load boosts the immune cell infiltration but does not significantly affect the expression of PD-L1 on tumor cells. The presence of neoantigens attract immune cells to tumor microenvironment but neoantigens do not contribute to significant increase in levels of PD-L1 expression on the tumor cells.

Editorial acknowledgement

Clinical trial identification

Legal entity responsible for the study

Datar Cancer Genetics.

Funding

Has not received any funding.

Disclosure

A.K. Vaid, N. Rohatgi: Non-Financial Interests, Personal, Advisory Board: Datar Cancer Genetics. V. Datta, R. Patil, S. Limaye: Financial Interests, Personal, Full or part-time Employment: Datar Cancer Genetics. All other authors have declared no conflicts of interest.