T-Cell Immunity Mechanisms in Cancer Immunotherapy

The immune system relies on T lymphocytes to recognise and eradicate malignant cells. CD8+ T cells scan peptide fragments displayed on major histocompatibility complex class I molecules at the tumour cell surface via their T cell receptor. Upon antigen recognition and co-stimulatory signalling, cytotoxic T cells release perforin and granzyme to induce apoptosis in cancer cells. Tumours may evade this surveillance through downregulation of antigen processing components such as TAP, loss of MHC class I expression and adoption of inhibitory ligands that engage immune checkpoints like PD-1 or CTLA-4. Checkpoint blockade antibodies have revolutionised therapy by restoring T cell effector functions in multiple malignancies. Meanwhile, strategies that augment antigenicity—through neoantigen vaccines, modulation of peptide transport or chemotherapeutic induction of novel epitopes—further expand the target repertoire for T cells. Adoptive transfer of tumour-infiltrating lymphocytes or genetically engineered T cells has demonstrated durable responses in select cancers. Integration of biomarker profiling, antigen processing augmentation and precise T cell engineering underpins the global advance of personalised immunotherapies. Current research continues to refine the balance between potent antitumour immunity and avoidance of autoimmunity, aiming to extend benefits across diverse patient populations and tumour types.

Research from Nature Portfolio

Exploratory biomarker analysis in paediatric patients receiving a PD-L1 inhibitor revealed that elevated CD8+ T cell infiltration, diverse T cell receptor repertoires and tertiary lymphoid structures correlate with favourable progression-free survival. Differential gene expression highlighted tumour neoantigen candidates driving these responses, guiding prospective profiling for checkpoint blockade. A novel approach to silence the antigen transporter TAP within tumours induced a consistent set of neoepitopes, enhancing MHC class I presentation and synergising with anti-PD-1 therapy to suppress tumour growth in multiple models. Combination of platinum-based chemotherapy with PD-1 blockade unveiled a repertoire of non-mutated neoantigens exposed by apoptotic tumour cells, eliciting robust multi-specific CD4+ and CD8+ T cell responses that associated with improved clinical outcomes. Collectively, these studies demonstrate that biomarker-driven patient selection, targeted modulation of antigen processing and chemotherapy-induced unveiling of antigens can be harnessed to potentiate T cell-mediated antitumour immunity.

T-Cell Immunity Mechanisms in Cancer Immunotherapy publication trend

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

Technical terms

T cell receptor (TCR): cell surface molecule on T lymphocytes that recognises peptide–MHC complexes and initiates antigen-specific activation.

Major histocompatibility complex class I (MHC class I): cell surface proteins that present intracellular peptide antigens to CD8+ T cells.

Neoantigen: novel peptide derived from tumour-specific mutations or aberrant processing that is recognised as non-self by T cells.

Transporter associated with antigen processing (TAP): protein complex that translocates cytosolic peptides into the endoplasmic reticulum for MHC class I loading.

Immune checkpoint: regulatory pathway such as PD-1 or CTLA-4 that dampens T cell activation to maintain self-tolerance and prevent autoimmunity.

Tumour-infiltrating lymphocyte (TIL): T cell that has migrated into the tumour microenvironment, often reflecting an ongoing antitumour immune response.

TEIPP antigens: non-mutated peptides presented by HLA class I molecules on tumours with impaired antigen processing, serving as alternative targets for CD8+ T cells.

References

1. Unleashing T cell anti-tumor immunity: new potential for 5-Nonloxytryptamine as an agent mediating MHC-I upregulation in tumors. Molecular Cancer (2023).
2. Multimodal immunogenomic biomarker analysis of tumors from pediatric patients enrolled to a phase 1-2 study of single-agent atezolizumab. Nature Cancer (2023).
3. Tumor-targeted silencing of the peptide transporter TAP induces potent antitumor immunity. Nature Communications (2019).
4. Combination of chemotherapy and PD-1 blockade induces T cell responses to tumor non-mutated neoantigens. Communications Biology (2020).
5. TEIPP antigens for T-cell based immunotherapy of immune-edited HLA class Ilow cancers. Molecular Immunology (2018).
6. Recent Advances in Targeting CD8 T-Cell Immunity for More Effective Cancer Immunotherapy. Frontiers in Immunology (2018).