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Life sciences · Journal article
Frontiers in Pharmacology · October 16, 2026
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Esophageal squamous cell carcinoma (ESCC) is associated with a poor prognosis, and the efficacy of conventional therapies (chemotherapy, radiotherapy, and surgery) remains limited. The advent of programmed death 1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors has substantially altered the treatment paradigm for ESCC. The combination of these immune checkpoint inhibitors (ICIs) with conventional treatments demonstrates significant synergistic potential. Standard oncological regimens often center on chemotherapy, radiotherapy, surgery, or various combinations thereof. This synergy stems from complementary mechanisms: conventional therapies can induce immunogenic cell death, release tumor antigens, and remodel the immunosuppressive tumor microenvironment, thereby laying the groundwork for immunotherapy. In turn, PD-1/PD-L1 inhibitors work by releasing the “brakes” on T cells, activating and enhancing the host anti-tumor immune response. This facilitates the elimination of residual cancer cells and establishes long-term immune surveillance. In conclusion, the combination of PD-1/PD-L1 inhibitors with conventional therapy achieves a greater-than-additive (“1 + 1>2”) effect and has evolved into a standard first-line treatment strategy for advanced/metastatic ESCC, substantially improving patient outcomes. Future research will focus on optimizing combination protocols, overcoming resistance, and precisely identifying patient populations most likely to benefit.