Abstract 121P
Background
Janus kinase (JAK) family, including JAK1/JAK2/JAK3, is intracellular non-receptor tyrosine kinase. Antigen-presenting protein beta-2-microglobulin (B2M) is a component of the human leukocyte antigen (HLA) class I molecule. Previous studies showed that loss of function mutations in JAK1/2/3 and B2M can lead to acquired resistance to PD-1 immunotherapy, which may be associated with the deficiency in the signaling pathways involved in interferon-receptor and in antigen presentation. Nevertheless, the relationship between different mutation type in JAK1/2/3 and B2M with other biomarkers for immunotherapy is unknown.
Methods
We divided the patients into two cohorts, three group for each. Two gene sets (JAK2 and JAK1/JAK2/JAK3/B2M) with three mutation status (wide type, likely loss-of-function and gain-of-function mutation) were compared. We retrospectively analyzed the difference of PD-L1 expression by immunohistochemical (IHC) staining using SP263 and tumor mutation burden (TMB) examined by 539 gene panel (Simceredx) sequencing. Results in TMB were also validated in TCGA datasets.
Results
Out of 1395 pan-cancer patients in JAK2 cohort, 13 patients carried gain-of-function mutations, of which nine were PD-L1 positive and four were PD-L1 negative. And five patients were found with loss-of-function mutations, which were all PD-L1 negative. Fisher’s exact test showed significant differences (P=0.021) in JAK2 three group. In JAK1/JAK2/JAK3/B2M cohort, the TMB was significantly different (P<0.01) between each two groups. The TMB of gain-of-function and loss-of-function group are higher than that of wide type. Similar results were verified in TCGA database.
Conclusions
This is the first report that the different mutation types in JAK2 and JAK1/2/3 and B2M are associated with different biomarkers for immunotherapy in solid tumors. As the relatively small population size and unclear mechanism, the conclusions of this study needed to be verified in a larger cohort.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.