TIM3+ breast cancer cells license immune evasion during micrometastasis outbreak Article Swipe
Catalina Rozalén
,
Irene Sangrador
,
Silvia Avalle
,
Sandra Blasco-Benito
,
Panagiota Tzortzi
,
María Sanz‐Flores
,
José Ángel Palomeque
,
Pau Torren-Duran
,
Mariona Dalmau Montalà
,
Héléna Brunel
,
Albert Coll-Manzano
,
Iván Pérez-Núñez
,
Tamara Martos
,
Sònia Servitja
,
Sandra Pérez‐Buira
,
José Ignacio Chacón
,
Ángel Guerrero‐Zotano
,
Eduardo Martínez de Dueñas
,
Yolanda Guillén
,
Laura Comerma
,
Begoña Bermejo
,
Anna Bigas
,
María Casanova-Acebes
,
Anna Alemany
,
Federico Rojo
,
Joan Albanell
,
Toni Celià-Terrassa
·
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1016/j.ccell.2025.06.015
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1016/j.ccell.2025.06.015
In metastasis, the dynamics of tumor-immune interactions during micrometastasis remain unclear. Identifying the vulnerabilities of micrometastases before outbreaking into macrometastases can reveal therapeutic opportunities for metastasis. Here, we report a function of T cell immunoglobulin and mucin domain 3 (TIM3) in tumor cells during micrometastasis using breast cancer (BC) metastasis mouse models. TIM3 is highly upregulated in micrometastases, promoting survival, stemness, and immune escape. TIM3+ tumor cells are specifically selected during early seeding of micrometastasis. Mechanistically, TIM3 increases β-catenin/interleukin-1β (IL-1β) signaling, leading to stemness and immune-evasion by inducing immunosuppressive γδ T cells and reducing CD8 T cells during micrometastasis. Clinical data confirm increased TIM3+ tumor cells in BC metastasis and TIM3+ tumor cells as a biomarker of poor outcome in BC patients. (Neo)adjuvant TIM3 blockade reduces the metastatic seeding and incidence in preclinical models. These findings unveil a specific mechanism of micrometastasis immune-evasion and the potential use of TIM3 blockade for subclinical metastasis.
Related Topics
Concepts
Micrometastasis
Metastasis
Immune system
Cancer research
Medicine
Cancer
Immunology
Internal medicine
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1016/j.ccell.2025.06.015
- OA Status
- hybrid
- Cited By
- 5
- References
- 100
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4412392653
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4412392653Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1016/j.ccell.2025.06.015Digital Object Identifier
- Title
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TIM3+ breast cancer cells license immune evasion during micrometastasis outbreakWork title
- Type
-
articleOpenAlex work type
- Language
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enPrimary language
- Publication year
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2025Year of publication
- Publication date
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2025-07-15Full publication date if available
- Authors
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Catalina Rozalén, Irene Sangrador, Silvia Avalle, Sandra Blasco-Benito, Panagiota Tzortzi, María Sanz‐Flores, José Ángel Palomeque, Pau Torren-Duran, Mariona Dalmau Montalà, Héléna Brunel, Albert Coll-Manzano, Iván Pérez-Núñez, Tamara Martos, Sònia Servitja, Sandra Pérez‐Buira, José Ignacio Chacón, Ángel Guerrero‐Zotano, Eduardo Martínez de Dueñas, Yolanda Guillén, Laura Comerma, Begoña Bermejo, Anna Bigas, María Casanova-Acebes, Anna Alemany, Federico Rojo, Joan Albanell, Toni Celià-TerrassaList of authors in order
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https://doi.org/10.1016/j.ccell.2025.06.015Publisher landing page
- Open access
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YesWhether a free full text is available
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hybridOpen access status per OpenAlex
- OA URL
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https://doi.org/10.1016/j.ccell.2025.06.015Direct OA link when available
- Concepts
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Micrometastasis, Metastasis, Immune system, Cancer research, Medicine, Cancer, Immunology, Internal medicineTop concepts (fields/topics) attached by OpenAlex
- Cited by
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5Total citation count in OpenAlex
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2025: 5Per-year citation counts (last 5 years)
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100Number of works referenced by this work
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10Other works algorithmically related by OpenAlex
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| referenced_works_count | 100 |
| abstract_inverted_index.3 | 38 |
| abstract_inverted_index.T | 32, 90, 95 |
| abstract_inverted_index.a | 29, 114, 137 |
| abstract_inverted_index.BC | 107, 120 |
| abstract_inverted_index.In | 0 |
| abstract_inverted_index.as | 113 |
| abstract_inverted_index.by | 86 |
| abstract_inverted_index.in | 40, 56, 106, 119, 131 |
| abstract_inverted_index.is | 53 |
| abstract_inverted_index.of | 4, 14, 31, 73, 116, 140, 147 |
| abstract_inverted_index.to | 82 |
| abstract_inverted_index.we | 27 |
| abstract_inverted_index.CD8 | 94 |
| abstract_inverted_index.and | 35, 61, 84, 92, 109, 129, 143 |
| abstract_inverted_index.are | 67 |
| abstract_inverted_index.can | 20 |
| abstract_inverted_index.for | 24, 150 |
| abstract_inverted_index.the | 2, 12, 126, 144 |
| abstract_inverted_index.use | 146 |
| abstract_inverted_index.(BC) | 48 |
| abstract_inverted_index.TIM3 | 52, 76, 123, 148 |
| abstract_inverted_index.cell | 33 |
| abstract_inverted_index.data | 100 |
| abstract_inverted_index.into | 18 |
| abstract_inverted_index.poor | 117 |
| abstract_inverted_index.γδ | 89 |
| abstract_inverted_index.Here, | 26 |
| abstract_inverted_index.These | 134 |
| abstract_inverted_index.cells | 42, 66, 91, 96, 105, 112 |
| abstract_inverted_index.early | 71 |
| abstract_inverted_index.mouse | 50 |
| abstract_inverted_index.mucin | 36 |
| abstract_inverted_index.tumor | 41, 65, 104, 111 |
| abstract_inverted_index.using | 45 |
| abstract_inverted_index.(TIM3) | 39 |
| abstract_inverted_index.before | 16 |
| abstract_inverted_index.breast | 46 |
| abstract_inverted_index.cancer | 47 |
| abstract_inverted_index.domain | 37 |
| abstract_inverted_index.during | 7, 43, 70, 97 |
| abstract_inverted_index.highly | 54 |
| abstract_inverted_index.immune | 62 |
| abstract_inverted_index.remain | 9 |
| abstract_inverted_index.report | 28 |
| abstract_inverted_index.reveal | 21 |
| abstract_inverted_index.unveil | 136 |
| abstract_inverted_index.confirm | 101 |
| abstract_inverted_index.escape. | 63 |
| abstract_inverted_index.leading | 81 |
| abstract_inverted_index.models. | 51, 133 |
| abstract_inverted_index.outcome | 118 |
| abstract_inverted_index.reduces | 125 |
| abstract_inverted_index.seeding | 72, 128 |
| abstract_inverted_index.(IL-1β) | 79 |
| abstract_inverted_index.Clinical | 99 |
| abstract_inverted_index.blockade | 124, 149 |
| abstract_inverted_index.dynamics | 3 |
| abstract_inverted_index.findings | 135 |
| abstract_inverted_index.function | 30 |
| abstract_inverted_index.inducing | 87 |
| abstract_inverted_index.reducing | 93 |
| abstract_inverted_index.selected | 69 |
| abstract_inverted_index.specific | 138 |
| abstract_inverted_index.stemness | 83 |
| abstract_inverted_index.unclear. | 10 |
| abstract_inverted_index.biomarker | 115 |
| abstract_inverted_index.incidence | 130 |
| abstract_inverted_index.increased | 102 |
| abstract_inverted_index.increases | 77 |
| abstract_inverted_index.mechanism | 139 |
| abstract_inverted_index.patients. | 121 |
| abstract_inverted_index.potential | 145 |
| abstract_inverted_index.promoting | 58 |
| abstract_inverted_index.stemness, | 60 |
| abstract_inverted_index.survival, | 59 |
| abstract_inverted_index.metastasis | 49, 108 |
| abstract_inverted_index.metastatic | 127 |
| abstract_inverted_index.signaling, | 80 |
| abstract_inverted_index.Identifying | 11 |
| abstract_inverted_index.metastasis, | 1 |
| abstract_inverted_index.metastasis. | 25, 152 |
| abstract_inverted_index.outbreaking | 17 |
| abstract_inverted_index.preclinical | 132 |
| abstract_inverted_index.subclinical | 151 |
| abstract_inverted_index.therapeutic | 22 |
| abstract_inverted_index.upregulated | 55 |
| abstract_inverted_index.interactions | 6 |
| abstract_inverted_index.specifically | 68 |
| abstract_inverted_index.tumor-immune | 5 |
| abstract_inverted_index.(Neo)adjuvant | 122 |
| abstract_inverted_index.opportunities | 23 |
| abstract_inverted_index.immune-evasion | 85, 142 |
| abstract_inverted_index.immunoglobulin | 34 |
| abstract_inverted_index.macrometastases | 19 |
| abstract_inverted_index.micrometastases | 15 |
| abstract_inverted_index.micrometastasis | 8, 44, 141 |
| abstract_inverted_index.vulnerabilities | 13 |
| abstract_inverted_index.Mechanistically, | 75 |
| abstract_inverted_index.TIM3<sup>+</sup> | 64, 103, 110 |
| abstract_inverted_index.micrometastases, | 57 |
| abstract_inverted_index.micrometastasis. | 74, 98 |
| abstract_inverted_index.immunosuppressive | 88 |
| abstract_inverted_index.β-catenin/interleukin-1β | 78 |
| cited_by_percentile_year.max | 98 |
| cited_by_percentile_year.min | 97 |
| countries_distinct_count | 2 |
| institutions_distinct_count | 27 |
| sustainable_development_goals[0].id | https://metadata.un.org/sdg/3 |
| sustainable_development_goals[0].score | 0.800000011920929 |
| sustainable_development_goals[0].display_name | Good health and well-being |
| citation_normalized_percentile.value | 0.97139455 |
| citation_normalized_percentile.is_in_top_1_percent | True |
| citation_normalized_percentile.is_in_top_10_percent | True |