T Cell Dynamics in Cancer Immunotherapy

T cells orchestrate adaptive antitumour responses through antigen recognition by the T cell receptor, followed by clonal expansion and differentiation into effector and memory subsets. In cancer immunotherapy, approaches such as checkpoint blockade, adoptive cell transfer and personalised vaccines aim to enhance T cell priming in lymphoid tissues, trafficking into the tumour microenvironment and sustained cytotoxic function. Chronic antigen exposure and suppressive signals within tumours drive T cell exhaustion and metabolic dysfunction, while co-stimulatory pathways and cytokine networks modulate proliferation and survival. Single-cell and high-dimensional profiling have uncovered functional heterogeneity among tumour-infiltrating lymphocytes, identifying subsets linked to therapeutic response or resistance. Integrating insights into cytokine signalling, co-inhibitory receptor expression and antigen-specific clonotypes is informing combination regimens and novel engineering strategies. A deeper mechanistic understanding of T cell dynamics across diverse malignancies is essential to extend the reach and durability of immunotherapy worldwide.

Research from Nature Portfolio

Recent work has shown that elevated prostaglandin E₂ within solid tumours impairs the expansion and survival of CD8+ tumour-infiltrating lymphocytes by disrupting interleukin-2 receptor assembly and downstream mTOR signalling. This lipid mediator downregulates the common γ chain of the IL-2 receptor, leading to defective metabolic adaptation, oxidative stress and ferroptotic cell death. Inhibition of PGE₂ receptors during ex vivo TIL expansion restores IL-2 responsiveness and enhances proliferation of tumour-reactive cells, resulting in improved tumour control in preclinical settings. In parallel, a machine-learning framework now predicts tumour-reactive T cell receptors directly from single-cell transcriptomic data, bypassing antigen screening. By integrating high-throughput TCR cloning with functional reactivity assays, this approach identifies candidate clonotypes with high specificity and sensitivity across cancer types, accelerating the generation of personalised T cell therapies.

T Cell Dynamics in Cancer Immunotherapy publication trend

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

Technical terms

T Cell Receptor (TCR): A specialised protein complex on the T cell surface that recognises peptide antigens presented by major histocompatibility complexes.

Tumour-Infiltrating Lymphocyte (TIL): A subset of T cells that migrate into and reside within tumour tissue, mediating local immune responses.

Immune Checkpoint Inhibitor: A therapeutic antibody that blocks inhibitory pathways in T cells, such as PD-1 or CTLA-4, to restore antitumour activity.

Neoantigen: A tumour-specific peptide arising from mutated proteins that is recognised as foreign by T cells.

Interleukin-2 (IL-2): A cytokine produced by activated T cells that drives proliferation, differentiation and survival of effector lymphocytes.

Clonal Expansion: The proliferation of T cells bearing identical TCRs following antigen recognition, amplifying a specific immune response.

References

1. PGE2 inhibits TIL expansion by disrupting IL-2 signalling and mitochondrial function. Nature (2024).
2. Prediction of tumor-reactive T cell receptors from scRNA-seq data for personalized T cell therapy. Nature Biotechnology (2024).
3. The activity and immune dynamics of PD-1 inhibition on high-risk pulmonary ground glass opacity lesions: insights from a single-arm, phase II trial. Signal Transduction and Targeted Therapy (2024).
4. The Tumor Microenvironment in the Response to Immune Checkpoint Blockade Therapies. Frontiers in Immunology (2020).