Browsing by Author "Almeida, Antonio M."
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- Flow cytometry and targeted immune transcriptomics identify distinct profiles in patients with chronic myeloid leukemia receiving tyrosine kinase inhibitors with or without interferon-αPublication . Alves, Raquel; McArdle, Stephanie E. B.; Vadakekolathu, Jayakumar; Gonçalves, Ana Cristina; Freitas-Tavares, Paulo; Pereira, Amélia; Almeida, Antonio M.; Sarmento-Ribeiro, Ana Bela; Rutella, SergioBACKGROUND: Tumor cells have evolved complex strategies to escape immune surveillance, a process which involves NK cells and T lymphocytes, and various immunological factors. Indeed, tumor cells recruit immunosuppressive cells [including regulatory T-cells (Treg), myeloid-derived suppressor cells (MDSC)] and express factors such as PD-L1. Molecularly targeted therapies, such as imatinib, have off-target effects that may influence immune function. Imatinib has been shown to modulate multiple cell types involved in anti-cancer immune surveillance, with potentially detrimental or favorable outcomes. Imatinib and other tyrosine kinase inhibitors (TKIs) in chronic myeloid leukemia (CML) have dramatically changed disease course. Our study aimed to characterize the different populations of the immune system in patients with CML affected by their treatment. METHODS: Forty-one patients with CML [33 treated with TKIs and 8 with TKIs plus interferon (IFN)-α] and 20 controls were enrolled in the present study. Peripheral blood populations of the immune system [referred to as the overview of immune system (OVIS) panel, Treg cells and MDSCs] and PD-1 expression were evaluated by flow cytometry. The immunological profile was assessed using the mRNA Pan-Cancer Immune Profiling Panel and a NanoString nCounter FLEX platform. RESULTS: Patients receiving combination therapy (TKIs + IFN-α) had lower numbers of lymphocytes, particularly T cells [838/µL (95% CI 594-1182)] compared with healthy controls [1500/µL (95% CI 1207 - 1865), p = 0.017]. These patients also had a higher percentage of Treg (9.1%) and CD4+PD-1+ cells (1.65%) compared with controls [Treg (6.1%) and CD4+/PD-1+(0.8%); p ≤ 0.05]. Moreover, patients treated with TKIs had more Mo-MDSCs (12.7%) whereas those treated with TKIs + IFN-α had more Gr-MDSC (21.3%) compared to controls [Mo-MDSC (11.4%) and Gr-MDSC (8.48%); p ≤ 0.05]. CD56bright NK cells, a cell subset endowed with immune-regulatory properties, were increased in patients receiving TKIs plus IFN-α compared with those treated with TKIs alone. Interestingly, serum IL-21 was significantly lower in the TKIs plus IFN-α cohort. Within the group of patients treated with TKI monotherapy, we observed that individuals receiving 2nd generation TKIs had lower percentages of CD4+ Treg (3.63%) and Gr-MDSC (4.2%) compared to patients under imatinib treatment (CD4+ Treg 6.18% and Gr-MDSC 8.2%), but higher levels of PD-1-co-expressing CD4+ cells (1.92%). CONCLUSIONS: Our results suggest that TKIs in combination with IFN-α may promote an enhanced immune suppressive state.
- Immune-monitoring of myelodysplastic neoplasms: recommendations from the i4MDS consortiumPublication . i4MDS consortium; Tentori, Cristina A.; Zhao, Lin P.; Tinterri, Benedetta; Strange, Kathryn E.; Zoldan, Katharina; Dimopoulos, Konstantinos; Feng, Xingmin; Riva, Elena; Lim, Benjamin; Simoni, Yannick; Murthy, Vidhya; Hayes, Madeline J.; Poloni, Antonella; Padron, Eric; Cardoso, Bruno A.; Cross, Michael; Winter, Susann; Santaolalla, Aida; Patel, Bhavisha A.; Groarke, Emma M.; Wiseman, Daniel H.; Jones, Katy; Jamieson, Lauren; Manogaran, Charles; Daver, Naval; Gallur, Laura; Ingram, Wendy; Ferrell, P. Brent; Sockel, Katja; Dulphy, Nicolas; Chapuis, Nicolas; Kubasch, Anne S.; Olsnes, Astrid M.; Kulasekararaj, Austin; Lavellade, Hugues De; Kern, Wolfgang; Hemelrijck, Mieke Van; Bonnet, Dominique; Westers, Theresia M.; Freeman, Sylvie; Oelschlaegel, Uta; Valcarcel, David; Raddi, Marco G.; Grønbæk, Kirsten; Fontenay, Michaela; Loghavi, Sanam; Santini, Valeria; Almeida, Antonio M.; Irish, Jonathan M.; Sallman, David A.; Young, Neal S.; Loosdrecht, Arjan A. van de; Adès, Lionel; Porta, Matteo G. Della; Cargo, Catherine; Platzbecker, Uwe; Kordasti, ShahramAdvancements in comprehending myelodysplastic neoplasms (MDS) have unfolded significantly in recent years, elucidating a myriad of cellular and molecular underpinnings integral to disease progression. While molecular inclusions into prognostic models have substantively advanced risk stratification, recent revelations have emphasized the pivotal role of immune dysregulation within the bone marrow milieu during MDS evolution. Nonetheless, immunotherapy for MDS has not experienced breakthroughs seen in other malignancies, partly attributable to the absence of an immune classification that could stratify patients toward optimally targeted immunotherapeutic approaches. A pivotal obstacle to establishing “immune classes” among MDS patients is the absence of validated accepted immune panels suitable for routine application in clinical laboratories. In response, we formed International Integrative Innovative Immunology for MDS (i4MDS), a consortium of multidisciplinary experts, and created the following recommendations for standardized methodologies to monitor immune responses in MDS. A central goal of i4MDS is the development of an immune score that could be incorporated into current clinical risk stratification models. This position paper first consolidates current knowledge on MDS immunology. Subsequently, in collaboration with clinical and laboratory specialists, we introduce flow cytometry panels and cytokine assays, meticulously devised for clinical laboratories, aiming to monitor the immune status of MDS patients, evaluating both immune fitness and identifying potential immune “risk factors.” By amalgamating this immunological characterization data and molecular data, we aim to enhance patient stratification, identify predictive markers for treatment responsiveness, and accelerate the development of systems immunology tools and innovative immunotherapies.