Immune-monitoring of myelodysplastic neoplasms: Recommendations from the i4MDS consortium.
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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, De Lavellade Hugues, Kern Wolfgang, Van Hemelrijck Mieke, 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, van de Loosdrecht Arjan A, Adès Lionel, Della Porta Matteo G, Cargo Catherine, Platzbecker Uwe, Kordasti Shahram, i4MDS consortium
Аннотация
Advancements 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.