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Post-lenalidomide immunomodulation in del(5q) MDS
Table 2. Lenalidomide-induced T-cell clusters.
Cluster (CDR3 sequence)
aPost-lenalidomide expansion (absolute normalized difference)
5.57E-05 3.71E-05 4.64E-05 3.71E-05 4.64E-05
1.86E-05 1.86E-05 5.57E-05 5.57E-05 1.86E-05 2.78E-05 1.86E-05 3.71E-05 3.71E-05 6.59E-04 3.71E-05 1.86E-05 2.78E-05 1.86E-05 1.86E-05 2.78E-05 3.71E-05 4.64E-05 2.78E-05 4.64E-05
Generation probability
31.88 31.23 30.77 30.06 29.69
36.74 36.74 36.74 36.74 36.74 36.74 36.74 36.74 36.04 35.64 35.64 35.64 34.95 34.79 34.43 34.25 34.10 33.60 33.56 33.07
Clusters with low generation probability shared by 3 patients
Clusters with low generation probability shared by 2 patients
CASREPSGGKPQHF
CATKDRDSNQPQHF CASSLWGGGDQPQHF CASSLGGLAGAEQFF CATSGSGRFYNEQFF
CASSQDFTDTQYF CASTEGRADTIYF CASSLGEGTAGYEQYF CASSPDGGRGGEQYF CAWSDRGLIGAFF CASSSSQAGTEAFF CASRSRDRGGDTF CASSLSAGVLSEQYF CASSSGPRQLFF CASSLGYPGSASYKQYF CASSQDSLSGYTF CSVEALGGATDTQYF CASSPRGVSGYTF CASSFPDREQYF CASSRDRGGVGEKLFF CASTSGLAVTGELFF CSASPRPGLAFF CASRPAGGRGEQFF CASTTAGAGQPQHF CASSPSTGGANVLTF
aThe absolute normalized difference is calculated by subtracting the cluster frequencies observed in baseline myelodysplastic syndrome (MDS) samples from those detected in MDS samples after lenalidomide treatment..
vation of novel lenalidomide-related T-cell clusters is rem- iniscent of recent data on response to PD-1 inhibitors fol- lowing failure of hypomethylating agent treatment.37,38 It has been shown that hypomethylating agent therapy leads to upregulation of PD-1 and PD-L1 in MDS BM cells, which may be an explanation of the sensitivity of a subset of MDS patients to immune checkpoint therapy after fail- ure of hypomethylating agent treatment. This concept has not yet been tested in lenalidomide-refractory MDS patients. Our data demonstrating emergence of novel T- cell clusters could, therefore, possibly serve as a novel pre- dictive marker for such a strategy, a possibility which war- rants further prospective evaluation. Identification of the
antigens recognized by the described lenalidomide- induced shared T-cell clusters could help in the design of novel immunotherapeutic approaches for del(5q) MDS.
Acknowledgments
The authors thank the “Hamburger Krebsgesellschaft” for financial support (grant to MB) and the Hubertus Wald Foundation for supporting a professorship (MB) for immunologi- cal cancer research and treatment. The authors also thank Janina Radloff and Barbara Goesch for their excellent technical assis- tance and Prof. Tanja Zeller for providing relevant material. DN is an endowed Professor of the Deutsche Jose Carreras Leukemia Stiftung (DJCLSH03/01).
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