Contributions
Abstract: EP416
Type: E-Poster Presentation
Session title: Acute myeloid leukemia - Biology & Translational Research
Background
Intensive chemotherapy (iCT) remains the main therapeutic option for a majority of patients with acute myeloid leukemia (AML). However, relapses are frequent and cause a high fatality rate, prompting the need for new therapeutic strategies, as well as a better stratification of patients to guide treatment choice. Multiple ongoing pre-clinical and clinical studies aim at harnessing the immune system against AML. Mucosal-Associated Invariant T cells (MAIT) constitute one of the largest subset of innate-like, cytotoxic T cell subsets in humans. A small but increasing number of papers suggest a role for MAIT cells in cancer but their functionality show different trends according to different studies.
Aims
In this study, we quantified circulating MAIT cells at diagnosis in a prospective cohort of newly diagnosed AML patients. We also monitored MAIT cells during intensive chemotherapy in a subset of these patients.
Methods
This study included patients with a newly diagnosed AML admitted at the Hematology department of Toulouse University Hospital-IUCT-O from 1st January 2015 to 31st October 2019. A written informed consent was obtained from all patients in accordance with the Declaration of Helsinki. All cytometry analyses were performed on fresh whole-blood lymphocytes and data were acquired on the Navios cytometer, and analyzed with the Kaluza software. Statistical analyses were performed with the Graphpad Prism software.
Results
We included 216 patients in this study. We observed a dramatic decrease of MAIT cell, compared to Healthy donors (p<0.0001). Whereas the relative proportions of CD4+ and CD8+ T cells were conserved in disease, the frequency of MAIT cells decreased importantly in AML patients (p<0.0001). In stark contrast, the percentage of activated MAIT was significantly higher in patients than controls (p=0.0065). We evaluated whether MAIT cells dynamics during this induction phase would differ, as compared with conventional CD4+ and CD8+ T cells. In our cohort, 25 patients were monitored at D15 post-induction, at the nadir of circulating lymphocyte numbers. The drop in MAIT cell numbers was more pronounced than for CD4+ (p<0.0001) and CD8+ T cells (p<0.001). We also obtained samples from 78 patients at D35 post-induction, which is the time point at which remission is evaluated, and leucopoiesis usually resumes. Indeed, at D35, CD4+ and CD8+ concentrations raised back to baseline levels, although CD4+ concentrations remained slightly lower than their D0 levels. MAIT cells showed the same trend, with no significant difference between pre- and post-treatment levels. We could obtain cytogenetic parameters in 207 (90.4%)patients and MAIT cells numbers dropped significantly according to the cytogenetic profile. Finally, we obtained at least partial mutation data for a total of 119/123 patients (96,7%) FLT3-ITD mutation were associated with higher numbers of CD4+, CD8+ and MAIT cells. IDH1/2 mutations were found in 29/118 patients (24.6%), and were associated with higher MAIT cell numbers only.
Conclusion
In this study we observed a significant MAIT cell deficiency in AML patients, which is differently associated with the cytogenetic and molecular profile of the patients, and the occurrence of complete remission after iCT.
Keyword(s): AML, Immunotherapy, T cell
Abstract: EP416
Type: E-Poster Presentation
Session title: Acute myeloid leukemia - Biology & Translational Research
Background
Intensive chemotherapy (iCT) remains the main therapeutic option for a majority of patients with acute myeloid leukemia (AML). However, relapses are frequent and cause a high fatality rate, prompting the need for new therapeutic strategies, as well as a better stratification of patients to guide treatment choice. Multiple ongoing pre-clinical and clinical studies aim at harnessing the immune system against AML. Mucosal-Associated Invariant T cells (MAIT) constitute one of the largest subset of innate-like, cytotoxic T cell subsets in humans. A small but increasing number of papers suggest a role for MAIT cells in cancer but their functionality show different trends according to different studies.
Aims
In this study, we quantified circulating MAIT cells at diagnosis in a prospective cohort of newly diagnosed AML patients. We also monitored MAIT cells during intensive chemotherapy in a subset of these patients.
Methods
This study included patients with a newly diagnosed AML admitted at the Hematology department of Toulouse University Hospital-IUCT-O from 1st January 2015 to 31st October 2019. A written informed consent was obtained from all patients in accordance with the Declaration of Helsinki. All cytometry analyses were performed on fresh whole-blood lymphocytes and data were acquired on the Navios cytometer, and analyzed with the Kaluza software. Statistical analyses were performed with the Graphpad Prism software.
Results
We included 216 patients in this study. We observed a dramatic decrease of MAIT cell, compared to Healthy donors (p<0.0001). Whereas the relative proportions of CD4+ and CD8+ T cells were conserved in disease, the frequency of MAIT cells decreased importantly in AML patients (p<0.0001). In stark contrast, the percentage of activated MAIT was significantly higher in patients than controls (p=0.0065). We evaluated whether MAIT cells dynamics during this induction phase would differ, as compared with conventional CD4+ and CD8+ T cells. In our cohort, 25 patients were monitored at D15 post-induction, at the nadir of circulating lymphocyte numbers. The drop in MAIT cell numbers was more pronounced than for CD4+ (p<0.0001) and CD8+ T cells (p<0.001). We also obtained samples from 78 patients at D35 post-induction, which is the time point at which remission is evaluated, and leucopoiesis usually resumes. Indeed, at D35, CD4+ and CD8+ concentrations raised back to baseline levels, although CD4+ concentrations remained slightly lower than their D0 levels. MAIT cells showed the same trend, with no significant difference between pre- and post-treatment levels. We could obtain cytogenetic parameters in 207 (90.4%)patients and MAIT cells numbers dropped significantly according to the cytogenetic profile. Finally, we obtained at least partial mutation data for a total of 119/123 patients (96,7%) FLT3-ITD mutation were associated with higher numbers of CD4+, CD8+ and MAIT cells. IDH1/2 mutations were found in 29/118 patients (24.6%), and were associated with higher MAIT cell numbers only.
Conclusion
In this study we observed a significant MAIT cell deficiency in AML patients, which is differently associated with the cytogenetic and molecular profile of the patients, and the occurrence of complete remission after iCT.
Keyword(s): AML, Immunotherapy, T cell