Wednesday, February 21, 2018

Very Brief Blog: Checkpoint Inhibitors in Hematological Malignancies (Open Access Review)

If you're like me, you think of checkpoint inhibitors first in solid tumors - melanoma, lung cancer, and so on.   Knowing less about it, I'm caught a bit off guard in the shift to leukemia/lymphoma therapy.

Chi Young Ok and Ken H Young provide a 16-page, open access, 2017 review of checkpoint inhibitors in J Hematol Oncol 10:103, 2017.   They're at MD Anderson.   Open access here.

There's cool stuff.  For example, PD-L1, PD-L2, and well known oncogene JAK2 are all at 9p24.  Who knew?  Errors as diverse as JAK2 upregulation, copy number and fusion events involving PD-L1, and 3'-untranslated region PD-L1 aberrations can all disrupt immuno surveillance in lymphomas.

For a non open access article with a quite different perspective based on B-cell malignancies, Muschen of City of Hope provides a perspective in Nature Reviews Cancer 18:103-116, 2018 (here).


Not related directly to heme tumors, but a NYT article today discusses rare variants of ovarian cancer that respond well to nivolumab where the majority of ovarian cancers don't.  The emerging rules about immunotherapy biomarkers (PDL1, TMB, etc) have strong exceptions and it's still being worked out (a point also made by Ok & Young).  {The NYT patient example is SSCOHT ovarian cancer driven by SMARCA4 mutations}.

Another "who knew?" interesting  Nature Reviews article recently pointed out the multiple ways that "regular" driver somatic mutations (EGFR, etc) also interplay with turning on immune evasion mechanisms (Seton-Rogers, Nat Rev Ca 18:67, 2018, here).