AbstractImmunohistochemical markers are associated with treatment outcome in
adults with classical Hodgkin Lymphoma (cHL). Studies in children are
scarce and inconsistent. We investigated in 67 children with cHL,
whether the expression of CD15, CD30, PAX5, PD-1, PD-L1, CD68, CD163 and
TARC is associated with the event-free survival (EFS) and the interim
remission status. Low expression of PD-L1 was significantly associated
with complete remission at interim PET-scan. There was no association
between marker expression and EFS. Our data suggest a difference between
pediatric and adult cHL. This underlies the importance of future
research into specific molecular drivers in pediatric cHL.
IntroductionClassical Hodgkin lymphoma (cHL) contains a notably small amount of
0.1-10% malignant Hodgkin and Reed-Sternberg (HRS) cells, surrounded by
inflammatory cells. These cells produce different cytokines and
chemokines, maintaining a specific tumor microenvironment (TME) in which
the HRS cells can thrive 1,2. There is a strong
variation among individual patients in the frequency and distribution of
HRS cells and the TME 3. These variations may be used
to identify prognostic markers in pediatric patients to develop
risk-adapted treatment strategies, leading to better outcome and less
treatment-related toxicities 1,2. Furthermore, these
markers could be new treatment targets. Multiple studies have
demonstrated that the presence of certain immune cell types and
immunohistochemical markers in the TME and on HRS cells is associated
with treatment outcome 4-7. However, most studies have
been performed in adult patients, and studies based on pediatric
populations are scarce and inconsistent 8-10. Previous
studies have shown differences in TME composition, PD-L1 expression, and
the role of Epstein Barr Virus (EBV) between pediatric and adult cHL
patients 10-14. Therefore, it is uncertain whether
outcomes of studies in adults with cHL are applicable to children with
cHL.
Therefore, we investigated the prognostic value of eight different
immunohistochemical markers in pediatric cHL. PD-1, PD-L1, CD15, CD30,
CD68 and CD163 have previously been analyzed in pediatric studies and
show conflicting outcomes 8-10,15. PAX5 and TARC were
chosen based on their prognostic impact in adult studies6,16,17.