Document resource
Background Advanced esophageal squamous cell carcinoma (ESCC) is associated with a dismal prognosis. While chemotherapy combined with immune checkpoint inhibitors (ICIs) offers a viable treatment option, there is a need to explore more effective strategies to address immune resistance. Recombinant human adenovirus type 5 (H101) is a genetically engineered oncolytic adenovirus. Although the combination of H101 and ICIs has demonstrated significant therapeutic benefits in overcoming immune resistance in both small cell lung cancer and non-small cell lung cancer, its application in the immunotherapy of ESCC patients remains underexplored.Methods We reported a case of a patient with multiple relapses of advanced ESCC who exhibited a progression-free survival (PFS) of 15.5 months following the administration of first-line chemotherapy in conjunction with immunotherapy. At first recurrence, the patient received H101 injection in metastatic lymph nodes with chemo- and immunotherapy, achieving a PFS of 30 months. During the second recurrence, after undergoing three cycles of the aforementioned combined treatment regimen, the patient experienced significant alleviation of their disease. Furthermore, we examined the potential molecular mechanisms underlying the effectiveness of H101 against ESCC using multiplex fluorescence analysis.Results The intralymphatic injection of H101 in conjunction with ICIs effectively reverses immune resistance in advanced ESCC. The only adverse effect observed during treatment was a transient fever, which may reflect the extent of the patient’s immune response activation. The fluorescence analysis results showed that the expression levels of CD3, CD4, CD8, CD20 and IL-1β in the cancer nest were all increased after two recurrences, indicating that the immune cell infiltration was increased and the immune microenvironment was effectively activated. In particular, we observed that during both relapses, IFN-γ levels exhibited a transient decrease at the initial phase of treatment (2 weeks), followed by a subsequent increase after one month of therapy. This dynamic alteration may be attributed to immunosuppressive mechanisms or immune cell exhaustion. The OVs could transiently suppress the tumor microenvironment during tumor cell lysis, potentially resulting in the temporary functional impairment of T cells and NK cells, consequently leading to a reduction in IFN-γ production.Conclusions Taken together, the intralymphatic injection of H101 combined with chemotherapy and immunotherapy may represent a promising clinical strategy for advanced ESCC patients with recurrent lymph node metastasis. Nevertheless, the efficacy and safety of H101 combination therapy in advanced ESCC needs to be validated through large-scale clinical trials in the future.Ethics Approval The study was conducted in accordance with the Declaration of Helsinki, and approved by the Institutional Review Board of the 900th Hospital of Joint Logistic Support Force (protocol code 2023-067).Consent A signed consent form was obtained from the patient, permitting the patient’s data to be presented as a case report.