Akoya Biosciences (AKYA) Status Update summary

Advances in spatial biology and cancer immunotherapy

• Spatial biology is transforming drug discovery and precision medicine, with a focus on understanding complex biological systems and optimizing therapeutic development.

• Tertiary lymphoid structures (TLS) have emerged as a key biomarker for predicting response to immune checkpoint inhibitors across multiple cancer types.

• In sarcoma, TLS presence correlates with improved outcomes and higher response rates to immunotherapy, as shown in both retrospective and prospective studies.

• TLS status is now used in routine pathology assessments, and standardized guidelines for evaluation have been published.

• The predictive value of TLS is universal across tumor types, not limited to sarcoma, and is independent of PD-L1 or CD8 expression.

Mechanisms and determinants of TLS in cancer

• High plasma cell abundance within TLS is most predictive of immunotherapy response, while high Treg infiltration is associated with resistance.

• Tumor mutational burden does not correlate with TLS formation; ongoing research aims to identify genomic and transcriptomic determinants.

• Fibroblast populations and immune checkpoint overexpression also contribute to resistance in TLS-positive tumors.

• Double immune checkpoint inhibition and targeting Treg cells are being explored to improve outcomes in TLS-positive cancers.

• Inducing TLS formation in TLS-negative tumors is a potential future strategy to enhance immunotherapy efficacy.

Clinical validation and implementation of TLS as a biomarker

• TLS can be assessed by pathologists using H&E slides and CD20/CD23 staining, with digital pathology and AI approaches under development.

• TLS assessment is now part of routine diagnostics for sarcoma and non-small cell lung cancer in some institutions.

• No significant structural or functional differences in TLS have been observed between sarcomas and other solid tumors; TLS remains a robust predictor of anti-tumor immune response.

• Ongoing and upcoming clinical trials are evaluating combination immunotherapies and further validating TLS as a universal biomarker.

• Guidelines for TLS evaluation have been published to standardize its use in clinical practice.