# Ambivalent Copper: Mechanistically Distinct Immune Effects Driving Innovation in Cancer Nanomedicine

## TL;DR

Copper has complex immune effects in cancer, offering new ways to improve immunotherapy by targeting tumors with copper-based nanomedicines.

## Contribution

The paper introduces Cu-based nanomedicines as a novel approach to modulate cancer immunity and enhance immunotherapy.

## Key findings

- Copper can both suppress and stimulate immune responses in cancer.
- Copper-based nanomedicines may convert 'cold' tumors into 'hot' ones, improving immunotherapy outcomes.
- Copper delivery could synergize with existing immunotherapies for better cancer treatment.

## Abstract

Copper (Cu) is an essential element required by all living cells, where it supports critical enzymatic and signaling functions. In cancer, this balance is often disrupted, creating vulnerabilities that can be therapeutically exploited. Changes in Cu availability have been shown to influence key immunoregulatory pathways, including those involved in inflammation, cell death, and immune evasion. Notably, Cu can drive expression of programmed death ligand 1 (PD-L1), contributing to immunosuppression, while also promoting immunogenic cell death, which stimulates adaptive immune responses. These dual effects highlight the complexity and therapeutic potential of Cu-based interventions, particularly in the context of immune modulation and toxicity. This review argues that Cu-based nanomedicines can selectively deliver high concentrations of bioactive Cu to tumor cells, inducing cell death and triggering adaptive immune responses. We summarize current knowledge on Cu’s roles in cancer and immunity, emphasizing recent insights into how these intersect through Cu-mediated modulation of anticancer immune pathways. Finally, we explore the clinical potential of Cu-based nanomedicines to convert immunologically “cold” tumors into “hot” ones, thereby improving responses to immunotherapy. Realizing this potential will depend on the thoughtful integration of Cu delivery approaches with existing immunotherapeutic strategies.