T Cell Immunity Modulation in Cancer Therapy

T cells are central to the immune system’s ability to recognise and eliminate malignant cells. In cancer therapy, modulation of T cell immunity encompasses strategies to enhance tumour-specific cytotoxic responses while overcoming mechanisms of immune evasion. Key approaches include blockade of inhibitory receptors, such as PD-1 and TIGIT, to reverse T cell exhaustion; agonism of co-stimulatory pathways, such as CD28 and CD226, to amplify effector function; and adoptive transfer of engineered T cells, including chimeric antigen receptor (CAR-T) cells, designed for improved tumour infiltration and persistence. The tumour microenvironment further shapes T cell activity through immunosuppressive cell populations (for example regulatory T cells and tumour-associated macrophages), cytokine networks and metabolic barriers. Recent advances have elucidated molecular underpinnings of receptor signalling, rediscovered the importance of Fc receptor engagement in antibody design and unveiled nanoscale organisation of immune synapses. Together, these insights are driving next-generation combination therapies that aim to deliver durable tumour control with minimal off-target effects.

Research from Nature Portfolio

Recent studies have demonstrated that the efficacy of anti-PD-L1 therapy can be significantly enhanced by concurrent blockade of TIGIT. One investigation revealed that an anti-TIGIT antibody remodels the tumour microenvironment by engaging Fcγ receptors on macrophages and dendritic cells, thereby promoting a transition of exhausted effector CD8+ T cells towards a memory-like phenotype. Another report has shown that TIGIT directly inhibits T cell activation via ligand-induced nanoclusters at the immune synapse; these dense receptor clusters coalesce with T cell receptor microclusters and suppress cytokine secretion through an intracellular ITT-like motif, independent of competition with co-stimulatory receptors.

T Cell Immunity Modulation in Cancer Therapy publication trend

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

Technical terms

T cell exhaustion: A dysfunctional state characterised by reduced proliferation and cytokine production after chronic antigen stimulation.

Immune checkpoint: A receptor–ligand pair that negatively regulates T cell activation to maintain self-tolerance and prevent overactivation.

TIGIT: An inhibitory receptor on T cells and natural killer cells that binds CD155, delivering suppressive signals.

PD-1/PD-L1: A receptor–ligand immune checkpoint axis that limits T cell activity in peripheral tissues and tumours.

Fcγ receptor (FcγR): A receptor on myeloid cells that recognises the Fc domain of antibodies, modulating phagocytosis and antigen presentation.

Nanocluster: A dense assembly of receptors at the cell membrane, critical for signal initiation or inhibition at immune synapses.

CD226: A co-stimulatory receptor on T cells that competes with TIGIT for ligand binding, promoting T cell activation.

Regulatory T cell (Treg): A subset of CD4+ T cells that suppress immune responses to maintain tolerance and limit inflammation.

Immune synapse: The specialised contact point between a T cell and an antigen-presenting cell, facilitating directed signalling.

References

1. Anti-TIGIT antibody improves PD-L1 blockade through myeloid and Treg cells. Nature (2024).
2. TIGIT can inhibit T cell activation via ligation-induced nanoclusters, independent of CD226 co-stimulation. Nature Communications (2023).
3. Co-inhibition of TIGIT and PD-1/PD-L1 in Cancer Immunotherapy: Mechanisms and Clinical Trials. Molecular Cancer (2023).
4. Mechanistic convergence of the TIGIT and PD-1 inhibitory pathways necessitates co-blockade to optimize anti-tumor CD8+ T cell responses. Immunity (2022).
5. CD8+ CD226high T cells in liver metastases dictate the prognosis of colorectal cancer patients treated with chemotherapy and radical surgery. Cellular & Molecular Immunology (2023).