# SAA restricts T cell mediated anti-tumor immunity by limiting antigen presentation in lung cancer

## TL;DR

This study shows that SAA, a protein overexpressed in lung cancer, suppresses immune responses by limiting antigen presentation, and blocking SAA improves T cell activity against tumors.

## Contribution

The study identifies SAA as a novel immunosuppressive mediator in lung cancer and proposes SAA neutralization as a potential immunotherapy target.

## Key findings

- SAA impairs dendritic cell and macrophage activation, promoting an M2 phenotype with reduced antigen presentation.
- SAA overexpression in lung cancer cells reduces CD8+ T cell infiltration and cytotoxicity.
- SAA neutralization enhances CD8+ T cell activation and tumor control by restoring APC activity.

## Abstract

Serum amyloid A (SAA), an acute-phase pro-inflammatory protein, is overexpressed in several cancers and is involved in shaping pro-tumor responses. We have previously reported that lung cancer stem cells secrete SAA, which contributes to tumor progression by inhibition of TH1 immunity. Here, we extended our studies to examine the mechanism of SAA mediated immunosuppression in both antigen-presenting cells (APCs) and the subsequent activation of T cells.

Using ex vivo co-culture systems and in vivo mice models, we found that SAA impaired dendritic cell and macrophage activation and drove macrophages toward an M2 phenotype with reduced antigen presentation. Lung cancer cells overexpressing SAA also consistently showed impaired CD8+ T cell infiltration and cytotoxicity, while SAA neutralization were efficient at enhancing CD8+ T cell activation and response to anti-tumor immunity. Mechanistically, we found that the immunosuppressive phenotype induced by SAA on APCs is mediated in part by CD36. Critically, inhibiting SAA by neutralization antibody recovered APC activity and enhanced T cell-dependent tumor control.

our results identify SAA as an important immunosuppressive mediator in the tumor microenvironment, implying that the SAA neutralizing antibody may be a potential target for the improvement of lung cancer immunotherapy.