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.