Induction of secondary cytotoxic T lymphocytes by liposomes containing HLA-DR antigens

Nature ◽  
1980 ◽  
Vol 283 (5746) ◽  
pp. 495-497 ◽  
Author(s):  
Steven J. Burakoff ◽  
Victor H. Engelhard ◽  
James Kaufman ◽  
Jack L. Strominger
Keyword(s):  
T Lymphocytes ◽  
Cytotoxic T Lymphocytes ◽  
Hla Dr

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 Possible involvement of the OKT4 molecule in T cell recognition of class II HLA antigens. Evidence from studies of cytotoxic T lymphocytes specific for SB antigens.

1982 ◽  
Vol 156 (4) ◽  
pp. 1065-1076 ◽  
Author(s):  
W E Biddison ◽  
P E Rao ◽  
M A Talle ◽  
G Goldstein ◽  
S Shaw
Keyword(s):  
T Cell ◽  
T Lymphocytes ◽  
Cytotoxic T Lymphocytes ◽  
Hla Antigens ◽  
Surface Expression ◽  
T Cell Differentiation ◽  
T Cell Recognition ◽  
Hla Dr ◽  
Specific Cytotoxicity ◽  
Functional Involvement

A recently described HLA gene, SB, which maps between GLO and HLA-DR, codes for Ia-like molecules that are similar to but distinct from HLA-DR molecules. Cytotoxic T lymphocytes (CTL) specific for SB1, SB2, SB3, and SB4 were compared with HLA-A2-specific CTL with respect to their surface expression of the T cell differentiation antigens OKT3, OKT4, and OKT8. All CTL activity was eliminated by treatment with OKT3 and C'. The SB-specific cytotoxicity was eliminated by OKT4 plus C' but not by OKT8 plus C'. In contrast, HLA-A2-specific killing was completely susceptible to treatment with OKT8 plus C' but not with OKT4 plus C'. Cytotoxicity was analyzed in the presence of OKT8 and a series of monoclonal antibodies (OKT4A, 4B, 4C, and 4D) that react with distinct epitopes on the OKT4 molecule. SB1-, SB3-, and SB4-specific CTL were partially inhibited by OKT4A and 4B (45-75%), whereas HLA-A2-specific CTL were partially inhibited by OKT8 (48-63%) but not by OKT4. SB2-specific CTL were not inhibited (less than 26%) by OKT8 or by any of the OKT4-related antibodies. These results suggest that the OKT4 marker may be expressed on most T cells that recognize allogeneic Ia or self Ia plus foreign antigens; OKT4+ cells do not appear to be functionally homogeneous in that they can act both as helper/inducer and cytotoxic cells. Models are proposed for the functional involvement of the OKT4 molecule in T cell-Ia antigen interactions.

HLA-DR Expression on Cytotoxic T Lymphocytes

1985 ◽  
Vol 22 (5) ◽  
pp. 455-461 ◽  
Author(s):  
S. R. RESS ◽  
G. STRASSMANN ◽  
F. H. BACH
Keyword(s):  
T Lymphocytes ◽  
Cytotoxic T Lymphocytes ◽  
Hla Dr

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.

Induction of antigen-specific CD4+ HLA-DR-restricted cytotoxic T lymphocytes as well as nonspecific nonrestricted killer cells by the recombinant mycobacterial 65-kDa heat-shock protein

1990 ◽  
Vol 20 (2) ◽  
pp. 369-377 ◽  
Author(s):  
Birhane Kale Ab ◽  
Rolf Kiessling ◽  
Jan D. A. Van Embden ◽  
Jelle E. R. Thole ◽  
Dinakantha S. Kumararatne ◽  
...  
Keyword(s):  
Heat Shock ◽  
T Lymphocytes ◽  
Heat Shock Protein ◽  
Cytotoxic T Lymphocytes ◽  
Killer Cells ◽  
Hla Dr

scholarly journals Association of Ovarian Tumor Epithelium Coexpressing HLA-DR and CA-125 Antigens with Tumor Infiltrating Cytotoxic T Lymphocytes

2003 ◽  
Vol 70 (1) ◽  
pp. 40-44 ◽  
Author(s):  
Norihiro Matsushita ◽  
Mohammad Ghazizadeh ◽  
Hideki Konishi ◽  
Tsutomu Araki
Keyword(s):  
T Lymphocytes ◽  
Cytotoxic T Lymphocytes ◽  
Ovarian Tumor ◽  
Ca 125 ◽  
Hla Dr

scholarly journals CHANGES IN THE IMMUNE STATUS OF PATIENTS WITH METASTATIC SOLID TUMORS DURING STEREOTACTIC RADIATION THERAPY

2020 ◽  
Vol 66 (3) ◽  
pp. 277-282
Author(s):  
Anton Zozulya ◽  
Sergey Novikov ◽  
Irina Baldueva ◽  
D. Girdyuk ◽  
Natalya Yemelyanova ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
T Lymphocytes ◽  
Solid Tumors ◽  
Cytotoxic T Lymphocytes ◽  
Malignant Tumors ◽  
Immunological Parameters ◽  
Stereotactic Radiation ◽  
Metastatic Lesions ◽  
Hla Dr ◽  
T Helpers

Purpose. To evaluate immunological status in patients with metastatic forms of solid tumors before and at different intervals after stereotactic body radiation therapy (SBRT) of metastatic lesions. Materials and methods. A quantitative assessment and analysis of blood immunological parameters was conducted before irradiation, after 3-4 weeks and 6-8 weeks after SBRT in patients with malignant tumors with oligometastases in the liver and lungs. All peripheral blood samples were analyzed by flow cytometry. Statistical analysis was performed using Friedman and Nemenyi criteria. Results. 3-4 weeks after the end of SBRT, we observed statistically significant increase of T-lymphocytes (CD3+CD19-); T-helpers (CD3+CD4+); activated T-helpers (CD3+CD4+HLA-DR+); activated cytotoxic T-lymphocytes (CD3+CD8+HLA-DR+) and decrease of B-lymphocytes (CD3-CD19+). Subsequently, after 6-8 weeks after the end of irradiation we detected decrease of T-lymphocytes (CD3+CD19-) and continuing increase in activated T-helpers (CD3+CD4+HLA-DR+) and activated cytotoxic T-lymphocytes (CD3+CD8+HLA-DR+). Conclusion. Thus, revealed dynamics of immunological parameters indicates the induction of the T-cell link of antitumor immunity against decreasing of indicators of humoral immunity.

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