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Immune analysis of lymph nodes in relation to the presence or absence of tumor infiltrating lymphocytes in triple-negative breast cancer
- Source :
- European Journal of Cancer, r-IGTP. Repositorio Institucional de Producción Científica del Instituto de Investigación Germans Trias i Pujol, instname, UPCommons. Portal del coneixement obert de la UPC, Universitat Politècnica de Catalunya (UPC)
- Publication Year :
- 2021
- Publisher :
- Elsevier BV, 2021.
-
Abstract
- Triple-negative breast cancer (TNBC) is a subtype of breast cancer with unmet medical needs. Several studies have proved that high levels of tumor infiltrating lymphocytes (TILs) at diagnosis of TNBC confer better prognosis and patients respond better to specific chemotherapies. Nonetheless, current evidence suggests that only 15% of TNBC patients have very high levels of TILs, and another 15% lacks TILs. One possible reason to explain why patients have low TILs at diagnosis is that lymphocytes might be deactivated by an immune checkpoint in local lymph nodes, provoking their retention in there as they are unresponsive to other immune stimuli. We have identified 15 high TILs (≥50%) and 20 low TILs (≤5%) TNBC patients with localised tumour (T1c-T2N0M0) and compared the protein expression of five immune checkpoints in lymph nodes. We have also performed a customised 50-immune gene NanoString expression panel, the NanoString 360 Breast Cancer panel, and whole exome sequencing for mutation and neoantigen load analyses. In low TILs, we observed higher expression of CTLA-4 in local lymph nodes, which could explain why lymphocytes get retained in there and do not migrate to tumour. These patients have also higher neoantigen load and higher expression of B7.H3 and B7.H4 in the tumour. In high TILs, we observed more PD-L1+ tumour cells and more expanded humoral response. These results could provide a strategy to revert low tumour immune infiltration at diagnosis of TNBC, improving their prognosis. This project was supported by a grant from INTHEOS Foundation, thanks to the donation received from Pompadour, and from FERO Foundation. Peer Reviewed "Article signat per 18 autors/es: Ángela Quintana, Vicente Peg, Aleix Prat, Teresa Moliné, Guillermo Villacampa, Laia Paré, Patricia Galván, Rodrigo Dientsmann, Peter Schmid, Giuseppe Curigliano, Eva Muñoz-Couselo, José Perez-Garcia, Merce Marti, Juan Blanco-Heredia, Carla dos Anjos, Miguel Vazquez, Leticia De Mattos-Arruda, Javier Cortés"
- Subjects :
- Adult
Informàtica::Aplicacions de la informàtica::Bioinformàtica [Àrees temàtiques de la UPC]
0301 basic medicine
Cancer Research
Triple Negative Breast Neoplasms
chemical and pharmacologic phenomena
medicine.disease_cause
Immune checkpoint inhibitors
03 medical and health sciences
Lymphocytes, Tumor-Infiltrating
0302 clinical medicine
Immune system
Breast cancer
Triple-negative breast cancer
Biomarkers, Tumor
Humans
Medicine
Càncer
Lymph nodes
Càncer -- Aspectes genètics
Exome sequencing
Aged
Neoantigens
Mutation
Tumor-infiltrating lymphocytes
business.industry
Gene Expression Profiling
hemic and immune systems
Middle Aged
Prognosis
medicine.disease
Immune checkpoint
Tumor infiltrating lymphocytes
030104 developmental biology
Oncology
Case-Control Studies
Breast--Cancer
030220 oncology & carcinogenesis
Cancer research
Female
Lymph Nodes
Lymph
business
Follow-Up Studies
Subjects
Details
- ISSN :
- 09598049
- Volume :
- 148
- Database :
- OpenAIRE
- Journal :
- European Journal of Cancer
- Accession number :
- edsair.doi.dedup.....072ce289166625648c2c8ef429e44f34