Reversing resistance to immune checkpoint inhibitor by adding recombinant human adenovirus type 5 in a patient with small cell lung cancer with promoted immune infiltration: a case report

Small cell lung cancer (SCLC) is an aggressive malignancy with poor prognosis. Since immune checkpoint inhibitors (ICIs) have had significant benefits in SCLC, studying and overcoming the mechanisms of ICI resistance have become critical. Oncolytic virotherapy has been demonstrated to improve the efficacy of anti-PD-1 therapy by favorably changing the tumor microenvironment. This suggests the potential of oncolytic virotherapy to overcome ICI resistance in SCLC. Herein, we report a patient with extensive-stage SCLC who underwent previous chemotherapy and ICI therapy since its recurrence. Because the disease progressed despite immunotherapy, we employed exploratory oncolytic therapy, which was able to successfully overcome ICI resistance with a considerable progression-free survival benefit of 9 months. This suggests that oncolytic virotherapy can considerably improve the antitumor efficacy of ICI therapy. We also observed changes in the infiltration of CD8 + T cells; the localization of CD8 + T cells tended change from "excluded" to "inflamed," and its abundance increased as treatment continued. This confirms favorable changes in the immune microenvironment. Our study proposed the potential benefit of adopting oncolytic virotherapy to overcome ICI resistance in patients with SCLC. We also revealed its impact on the immune microenvironment to guide future mechanistic investigations.