scholarly journals Expression of HLA-DR in Cytotoxic T Lymphocytes: A Validated Predictive Biomarker and a Potential Therapeutic Strategy in Breast Cancer

Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3841
Author(s):  
Diana P. Saraiva ◽  
Sofia Azeredo-Lopes ◽  
Ana Antunes ◽  
Rute Salvador ◽  
Paula Borralho ◽  
...  
Keyword(s):  
Breast Cancer ◽  
T Lymphocytes ◽  
Cytotoxic T Lymphocytes ◽  
Ex Vivo ◽  
Probability Model ◽  
Predictive Biomarkers ◽  
Progression Free Survival ◽  
Effective Response ◽  
Hla Dr ◽  
Potential Biomarker

Neoadjuvant chemotherapy (NACT) is common in breast cancer (BC) treatment, though more than half of the patients lack an effective response. Therefore, new predictive biomarkers and alternative therapies are crucial. Previously, we proposed HLA-DR-expressing cytotoxic T lymphocytes (CTLs) as a potential biomarker of the response to NACT. To validate this observation and further investigate these cells, 202 BC patients were enrolled. Flow cytometry analyses were performed in 61 biopsies and 41 blood samples pre-NACT and 100 non-NACT tumor samples. All the patients were followed up for 34 months. Blood-isolated immune cells were cultured with BC cell lines in a 3D system. We confirmed that HLA-DR level in CTLs is a highly sensitive, specific, and independent biomarker to predict response to NACT and developed a predictive probability model. This biomarker was also associated with progression-free survival, regardless of the treatment. The clinical observations are substantiated by the anti-tumor properties of HLA-DR-expressing CTLs. Intriguingly, HLA-DR level in CTLs can be modulated ex vivo, boosting their capacity to kill tumor cells synergistically with doxorubicin. Thus, HLA-DR expression in CTLs is a validated tool to select patients that will actually benefit from NACT, and its stimulation might be a novel therapeutic approach for BC.

scholarly journals Determination of HLA-DR level in cytotoxic T lymphocytes: a new validated tool to predict breast cancer response to treatment

2021 ◽  
Author(s):  
Diana P Saraiva ◽  
Sofia Azeredo-Lopes ◽  
Ana Antunes ◽  
Rute Salvador ◽  
Paula Borralho ◽  
...  
Keyword(s):  
Breast Cancer ◽  
T Lymphocytes ◽  
Cytotoxic T Lymphocytes ◽  
Locally Advanced ◽  
Predictive Biomarkers ◽  
Response To Treatment ◽  
Effective Response ◽  
Hla Dr ◽  
Therapeutic Decisions

Background: Neoadjuvant chemotherapy (NACT) is the usual treatment for locally-advanced breast cancer (BC). However, more than half of the patients lack an effective response to this treatment. Thus, it is urgent to find predictive biomarkers. Recently, we proposed the HLA-DR expression level in cytotoxic T lymphocytes (CTLs) as a robust biomarker to select, in advance, patients that will actually benefit from NACT. Patients and Methods: A total of 202 BC patients, 102 of which submitted to NACT, were enrolled in this study. 61 biopsies and 41 blood samples collected pre-NACT and 100 non-NACT tumor samples were immunophenotyped by flow cytometry. Both NACT and non-NACT patients were followed up for 34 months. Blood-isolated immune cells were cultured with BC cell lines in a 3D system. Results: Here we confirmed that HLA-DR level in CTLs is a highly sensitive and specific biomarker to predict BC response to NACT, reflected in circulation and independent of the patients age, BC subtype and other tumor-immunological features. Therefore, we developed a predictive probability model, based on the determination of HLA-DR level in tumor-infiltrating CTLs, that could be used to guide therapeutic decisions. Interestingly, this biomarker was also associated with progression-free survival, regardless the treatment. Contrary to HLA-DRnegative CTLs, HLA-DR+ CTLs were able to reduce the viability of tumor cells, in culture, in agreement with their higher expression of activation, proliferation and cytotoxicity-related molecules. Tissue-residency and memory markers were also increased in HLA-DR+ CTLs. These anti-tumor features of HLA-DR+ CTLs may justify the clinical observations. Conclusion: HLA-DR level in CTLs is a validated and independent biomarker to predict response to NACT which allow the establishment of a clinical meaningful tool to select in advance patients that will truly benefit from this treatment. Intriguingly, it may be further used as a biomarker of BC patients general prognosis.

Generation and ex vivo expansion of cytotoxic T lymphocytes directed toward different types of leukemia or myelodysplastic cells using both HLA-matched and partially matched donors

2003 ◽  
Vol 31 (11) ◽  
pp. 1031-1038 ◽  
Author(s):  
Daniela Montagna ◽  
Rita Maccario ◽  
Enrica Montini ◽  
Roberto Tonelli ◽  
Daniela Lisini ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
Cytotoxic T Lymphocytes ◽  
Ex Vivo ◽  
Ex Vivo Expansion ◽  
Different Types

Therapeutic Efficacy of MUC1-Specific Cytotoxic T Lymphocytes and CD137 Co-Stimulation in a Spontaneous Breast Cancer Model

2004 ◽  
Vol 20 (1) ◽  
pp. 53-63 ◽  
Author(s):  
Pinku Mukherjee ◽  
Teresa L. Tinder ◽  
Gargi D. Basu ◽  
Latha B. Pathangey ◽  
Lieping Chen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
T Lymphocytes ◽  
Cytotoxic T Lymphocytes ◽  
Therapeutic Efficacy ◽  
Cancer Model ◽  
Breast Cancer Model

Feasibility and safety of adoptive immunotherapy with ex vivo-generated autologous, cytotoxic T lymphocytes in patients with solid tumor

Cytotherapy ◽  
2012 ◽  
Vol 14 (1) ◽  
pp. 80-90 ◽  
Author(s):  
Daniela Montagna ◽  
Ilaria Turin ◽  
Roberta Schiavo ◽  
Enrica Montini ◽  
Nadia Zaffaroni ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
Cytotoxic T Lymphocytes ◽  
Adoptive Immunotherapy ◽  
Solid Tumor ◽  
Ex Vivo

scholarly journals The role of abemaciclib in treatment of advanced breast cancer

2018 ◽  
Vol 10 ◽  
pp. 175883591877692 ◽  
Author(s):  
Amelia McCartney ◽  
Erica Moretti ◽  
Giuseppina Sanna ◽  
Marta Pestrin ◽  
Emanuela Risi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Advanced Breast Cancer ◽  
Single Agent ◽  
Endocrine Resistance ◽  
Predictive Biomarkers ◽  
Progression Free Survival ◽  
Advanced Breast ◽  
Significant Activity ◽  
Epidermal Growth

Until recently, the mainstay of treatment in the majority of hormone receptor (HR)-positive, human epidermal growth factor 2 receptor (HER2)-negative advanced breast cancer (ABC) has consisted of single-agent endocrine therapy (ET). However, as understanding of endocrine resistance has grown, newer targeted agents have come to the fore. Inhibition of cyclin-dependent kinase complexes 4 and 6 (CDK4/6) combined with ET has shown significant activity in HR+ HER2− ABC, with impressive results in terms of progression-free survival (PFS) when compared with ET alone. This review summarizes the seminal findings pertaining to CDK4/6 inhibition in this population, specifically focusing on abemaciclib, contrasted with palbociclib and ribociclib. Potential directions for future studies are discussed, as a way of addressing outstanding issues such as establishing optimal treatment sequencing and agent combinations, appropriate patient selection to derive maximal benefits, predictive biomarkers and the employment of CDK4/6 inhibition beyond the ABC setting.

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