Tumour Immunology

Tumour immunology examines how the host immune system recognises, restrains and sometimes inadvertently promotes cancer. Early on, transformed cells are detected and eliminated by innate effectors such as natural killer cells and macrophages, a process known as immunosurveillance. If malignant cells persist, adaptive responses engage, with dendritic cells presenting tumour antigens to T lymphocytes and B lymphocytes generating antitumour antibodies. Throughout tumour evolution, a dynamic immunoediting process—comprising elimination, equilibrium and escape—shapes the antigenic landscape. Cancer cells acquire mechanisms to evade detection: downregulating antigen presentation machinery, secreting immunosuppressive cytokines (for example interleukin-10 and transforming growth factor-β) and recruiting regulatory populations such as myeloid-derived suppressor cells and regulatory T cells. Moreover, the tumour microenvironment, characterised by hypoxia and metabolic competition, can drive T-cell exhaustion and promote tumour progression. Understanding the interplay between immune effectors and the immunosuppressive niche underpins current and emerging cancer therapies.

Research from Nature Portfolio

Combined blockade of programmed death-ligand 1 and transforming growth factor-β has been shown in murine carcinoma models to reinvigorate antitumour T-cells. A single bifunctional antibody targeting PD-L1 fused to a TGF-β trap expanded stem cell-like CD8⁺ T-cell subsets within immune-excluded tumours, promoted interferon-γ signalling and restored T-cell motility and tumour infiltration more effectively than monotherapies. This dual-target approach also attenuated regulatory T-cell accumulation and remodelled the stromal and myeloid compartments to support robust cytotoxic responses. In parallel, a dietary lipid, trans-vaccenic acid, was shown to reprogramme CD8⁺ T-cell effector function and antitumour activity in vivo. Mechanistically, this fatty acid antagonises G protein-coupled receptors EP2 and EP4 on T cells, triggering a cAMP–PKA–CREB signalling axis that enhances proliferation and cytotoxicity. These studies illustrate how mechanistic insights into immune checkpoints and nutrient sensing can be harnessed for next-generation immunotherapies.

Research from all publishers

A deep learning-based digital pathology algorithm has been developed to quantify tumour-infiltrating lymphocytes (TILs) on routine haematoxylin and eosin sections. By generating an electronic TIL score (eTIL) as a continuous measure of lymphocyte density, this approach demonstrated prognostic value in primary melanoma and predicted response to PD-1 checkpoint blockade in metastatic lesions. Integration of eTIL with staging improved risk stratification and identified patients likely to benefit from immunotherapy.

In malignant pleural effusion, C-C motif chemokine ligand 11 (CCL11)–CCR3-dependent eosinophilia has emerged as a protective immune mechanism. Studies in human samples and mouse models showed that tumour-derived signals induced eosinophil migration into the pleural space, where these cells modulated local cytokine networks and restricted fluid accumulation. Augmenting eosinophil numbers by adoptive transfer or chemokine agonism improved effusion dynamics and survival, highlighting eosinophils as potential effectors in cancer-associated inflammation.

Tumour Immunology publication trend

The graph below shows the total number of articles in tumour immunology across all publications each year (not limited to Nature Index journals).

Technical terms

Tumour microenvironment: The complex milieu of cancer cells, stromal elements, immune infiltrates, extracellular matrix and soluble factors that influences tumour growth, invasion and therapy response.

Tumour-infiltrating lymphocytes (TILs): Antigen-experienced T cells that have migrated into and reside within tumour tissue, reflecting antitumour immune activity.

Immune checkpoint blockade (ICB): Therapeutic inhibition of inhibitory receptor–ligand interactions (for example PD-1/PD-L1 or CTLA-4/B7) to restore T-cell-mediated antitumour responses.

Stem cell-like CD8⁺ T cell (T_SCL): A progenitor subset of CD8⁺ T cells with self-renewal capacity that differentiates into effector cells upon checkpoint inhibition, sustaining long-term immunity.

Electronic TIL score (eTIL): A digital pathology-derived continuous percentage measure of lymphocyte density within tumour areas, used as a prognostic and predictive biomarker.

CCL11/CCR3-dependent eosinophilia: Recruitment of eosinophils to tumour or effusion sites driven by the chemokine CCL11 and its receptor CCR3, mediating protective effects in cancer-associated fluid accumulation.

References

1. Combined PD-L1/TGFβ blockade allows expansion and differentiation of stem cell-like CD8 T cells in immune excluded tumors. Nature Communications (2023).
2. Trans-vaccenic acid reprograms CD8+ T cells and anti-tumour immunity. Nature (2023).
3. Deep learning-based scoring of tumour-infiltrating lymphocytes is prognostic in primary melanoma and predictive to PD-1 checkpoint inhibition in melanoma metastases. EBioMedicine (2023).
4. CCL11/CCR3-dependent eosinophilia alleviates malignant pleural effusions and improves prognosis. npj Precision Oncology (2024).