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Despite extensive research no meaningful progress in systemic treatment of small cell lung cancer
(SCLC) has been made in the past decades. Earlier attempts with immunotherapy including interferon and
vaccination approaches had limited success. High mutational load, smoking history and potentially also
the frequent presence of paraneoplastic phenomena—indicating an activated immune system—represent a
rationale for a benefit from immune checkpoint inhibitors in SCLC. However, the likelihood of response
is diminished due to poor T-cell activation resulting from low expression of MHC class I antigens, low
amounts of tumor infiltrating lymphocytes (TILs) and low PD-L1 expression rates. Recently, early reports
from studies with checkpoint inhibitors have shown promising results with the potential for long term
disease control in a subset of SCLC patients. However, reliable predictive biomarkers to better define the
population drawing most benefit are currently lacking. Results from ongoing phase III trials in different
treatment lines and in the maintenance setting are eagerly awaited.