Mechanisms regulating T-cell infiltration and activity in solid tumors
Open accessAbstract
T-lymphocytes play a critical role in cancer immunity as evidenced by their presence in resected tumor samples derived from long-surviving patients, and impressive clinical responses to various immunotherapies that reinvigorate them. Indeed, tumors can upregulate a wide array of defense mechanisms, both direct and indirect, to suppress the ability of Tcells to reach the tumor bed and mount curative responses upon infiltration. In addition, patient and tumor genetics, previous antigenic experience, and the microbiome, are all important factors in shaping the T-cell repertoire and sensitivity to immunotherapy. Here, we review the mechanisms that regulate T-cell homing, infiltration, and activity within the solid tumor bed. Finally, we summarize different immunotherapies and combinatorial treatment strategies that enable the immune system to overcome barriers for enhanced tumor control and improved patient outcome.
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The Trp-Kyn-AhR pathway is one mediator of immunosuppression in T cell-inflamed tumors.
“one mediator of immunosuppression in T cell-inflamed tumors is the tryptophan-kynurenine-aryl hydrocarbon receptor (Trp-Kyn-AhR) pathway.”
From Reimagining IDO Pathway Inhibition in Cancer Immunotherapy via Downstream Focus on the Tryptophan–Kynurenine–Aryl Hydrocarbon Axis (2019) · cites this paper as [14]
Preclinical studies identified multiple immunosuppressive mechanisms in T cell-inflamed tumors, including FoxP3-positive regulatory T cells and the Trp-Kyn-AhR pathway.
“Preclinical studies have identified multiple immunosuppressive mechanisms that are present in the T cell inflamed tumors, including, but not limited to, extrinsic inhibition by regulatory cell populations such as forkhead box P3 (FoxP3)-positive regulatory T cells (Tregs) and metabolic mechanisms of immune suppression such as the tryptophan-kynurenine-aryl hydrocarbon receptor (Trp-Kyn-AhR) path”
From Reimagining IDO Pathway Inhibition in Cancer Immunotherapy via Downstream Focus on the Tryptophan–Kynurenine–Aryl Hydrocarbon Axis (2019) · cites this paper as [14]
Despite robust T cell inflammation, a considerable percentage of tumors progress due to multiple immunosuppressive mechanisms.
“However, despite robust T cell inflammation, a considerable percentage of tumors progress by virtue of multiple immuno-suppressive mechanisms (14,15).”
From Reimagining IDO Pathway Inhibition in Cancer Immunotherapy via Downstream Focus on the Tryptophan–Kynurenine–Aryl Hydrocarbon Axis (2019) · cites this paper as [14]
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References 307 · Cited by 369
- Authors
- Lanitis, E., Dangaj, D., Irving, M., & Coukos, G.
- Affiliations
- Ludwig Cancer Research (CH)
- Centre Hospitalier Universitaire Vaudois (CH)
- Corresponding author
- Coukos, G.
- Venue
- Annals of Oncology
- Publisher
- Elsevier BV
- Published
- 2017-12
- Volume
- 28
- Issue
- suppl_12
- Pages
- xii18-xii32
- ISSN
- 0923-7534 (ISSN-L)
- OpenAlex
- W2760638321
- Cited by
- 369
- References
- 307
- Citations by year
- 2026: 18 · 2025: 28 · 2024: 41 · 2023: 59 · 2022: 48 · 2021: 52 · 2020: 56 · 2019: 41 · 2018: 23 · 2017: 3
- FWCI
- 14.83
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Annals of Oncology (publishedVersion)
- PubMed (publishedVersion)
- IRIS (submittedVersion)
- SERVAL (Université de Lausanne) (submittedVersion)
- Funders
- European Research Council (1400206AdG-322875)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Keywords
- T cell infiltration, solid tumors, T cell homing, tumor immune evasion, cancer immunotherapy, T cell receptor repertoire, tumor microbiome, immunotherapy resistance, combination therapy, tumor microenvironment
- MeSH terms
- Humans, Immunotherapy, Neoplasms, T-Lymphocytes, Lymphocytes, Tumor-Infiltrating
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