Introduction
Despite the fact that esophageal
cancer is one of the deadliest cancers in the world, there are fewer
drugs that have been proven to be effective against esophageal cancer
than against cancers at other sites. In the United States and Europe,
adenocarcinoma is the most common histological type, and chemotherapy
regimens are often selected in a manner similar to that for gastric
cancer. On the other hand, squamous cell carcinoma is the main
histological type in Asia, and the combination of cisplatin and
5-fluorouracil has been used as a key approach in Japan.
With the clinical success of immune checkpoint inhibitors (ICIs), such
as anti-PD-1 and anti-CTLA-4 antibodies, tumor immunity has attracted
much attention in cancer treatment. In the 2000s, it became clear that
immunity against tumors plays an important role in not only suppressing
cancer development but also cell-killing anticancer therapies, such as
radiotherapy (RT) and
chemotherapy.
The ATTRACTION-3 study is a phase III clinical trial with unresectable
advanced or recurrent esophageal cancer that is refractory or intolerant
to combination chemotherapy (1). Nivolumab showed a significant increase
in survival compared with chemotherapy (taxane), and then, nivolumab was
approved as a second-line treatment for unresectable advanced,
recurrent, or metastatic esophageal squamous cell carcinoma (ESCC) by
the Food and Drug Administration. and for unresectable advanced,
recurrent, or metastatic esophageal cancer by the Pharmaceuticals and
Medical Devices Agency, Japan, in 2020. However, the response rate was
only 19%. The combination of nivolumab with other therapies to enhance
its efficacy is being actively studied worldwide. Recently, the results
of the CheckMate 648 Trial, a phase III clinical trial involving
nivolumab combination therapy as a first-line treatment in advanced ESCC
were reported (2). Nivolumab plus chemotherapy and nivolumab plus
ipilimumab resulted in significantly longer overall survival than
chemotherapy alone, with no new safety signals identified. However, the
median overall survival period was 13.7–15.4 months, and further
improvement in the treatment protocol is still needed.
A rare phenomenon called the
“abscopal effect” refers to the regression of not only the irradiated
tumor but also non-irradiated distant tumors after local RT. The
mechanism is not completely clear,
but it is thought that the activation of anti-tumor immunity induced by
RT is the main factor (3,4). Recently, the “abscopal effect” was
reported in patients treated with a combination of ICIs and RT (ICI+RT)
(5,6). Though the abscopal
effect is exceedingly rare in
esophageal cancer, some reports were recently published (7,8).
Here, we report a patient with anti-PD-1 monoclonal antibody
(mAb)-resistant ESCC showing the abscopal effect (systemic response),
and present the findings of T-cell receptor (TCR) and B-cell receptor
(BCR) repertoire analysis before and after RT.