Targeting Immune Modulation in Cancer Therapy

Advances in cancer therapy increasingly harness the body’s own defences by reshaping immune responses within the tumour microenvironment. Tumours exploit regulatory pathways known as immune checkpoints to evade detection, promote an immunosuppressive niche and blunt T-cell activity. By inhibiting these checkpoints or blocking suppressive signals, it is possible to reinvigorate cytotoxic lymphocytes, enhance antigen presentation and disrupt pro-tumoural inflammation. Central to this approach is the recognition of phosphatidylserine exposure on dying or stressed cells as a suppressive cue, the manipulation of checkpoint receptors on T cells and macrophages, and the design of combination regimens that integrate chemotherapy, targeted antibodies and vaccine platforms. Globally significant in both solid and haematological malignancies, immune modulation has yielded durable remissions where conventional therapy fails and continues to broaden the spectrum of cancers amenable to immunological control.

Research from Nature Portfolio

Recent studies have demonstrated that annexin A5, when administered after cytotoxic treatment, binds externalized phosphatidylserine within the tumour microenvironment and prevents the formation of an immunosuppressive barrier. Coupling tumour antigens to annexin A5 enhances uptake by antigen-presenting cells and synergises with checkpoint inhibitors to produce robust T-cell–mediated tumour rejection. In parallel, a lipid-based vaccine platform combined with intermittent low-dose cyclophosphamide and anti-phosphatidylserine antibodies has been shown to increase infiltration by cytotoxic T cells, macrophages and dendritic cells. The addition of PD-1 blockade further augments cytotoxic gene expression and T-cell clonality within the tumour, highlighting the power of multi-modal immune modulation.

Targeting Immune Modulation in Cancer Therapy publication trend

The graph below shows the total number of articles in targeting immune modulation in cancer therapy across all publications each year (not limited to Nature Index journals).

Technical terms

Phosphatidylserine (PS): an anionic phospholipid normally confined to the inner leaflet of the plasma membrane, whose externalisation marks cells for removal and can signal immunosuppression in tumours.

Immune checkpoint: a regulatory node in the immune system that limits T-cell activation and prevents excessive inflammation, often co-opted by tumours to evade immune attack.

Tumour microenvironment (TME): the complex assembly of cancer cells, stromal elements, blood vessels and immune infiltrates that surrounds and influences tumour growth and therapy response.

Immune checkpoint inhibitor: a therapeutic agent—often a monoclonal antibody—that blocks checkpoint molecules such as PD-1 or CTLA-4 to restore anti-tumour T-cell function.

References

1. Phosphatidylserine: paving the way for a new era in cancer therapies. Materials Advances (2024).
2. Annexin A5 as an immune checkpoint inhibitor and tumor-homing molecule for cancer treatment. Nature Communications (2020).
3. Phosphatidylserine-targeting antibodies augment the anti-tumorigenic activity of anti-PD-1 therapy by enhancing immune activation and downregulating pro-oncogenic factors induced by T-cell checkpoint inhibition in murine triple-negative breast cancers. Breast Cancer Research (2016).
4. TIMs, TAMs, and PS- antibody targeting: implications for cancer immunotherapy. Cell Communication and Signaling (2020).
5. Anti-PD-1 increases the clonality and activity of tumor infiltrating antigen specific T cells induced by a potent immune therapy consisting of vaccine and metronomic cyclophosphamide. Journal for ImmunoTherapy of Cancer (2016).
6. Phosphatidylserine externalization as immune checkpoint in cancer. Pflügers Archiv - European Journal of Physiology (2024).