Comparison between traditional chemotherapy and chemoimmunotherapy. Traditional standard chemotherapy contained alkylating agents, platinum, antimetabolites, microtubule inhibitors, and so on. Each of them attacks malignant cells directly through particular mechanism. For example, alkylating agents and platinum combine with DNA to break it. Antimetabolites, for instance, 5-fluorouracil is similar to certain metabolites of nucleic acid and protein in our body, which would combine with each other and influence or antagonize relative metabolic processes of tumor cells. Microtubule inhibitors, such as paclitaxel, induce the termination of mitosis in tumor cells by suppress decondensation of tubulin. The combination of immunotherapy and chemotherapy (Chemoimmunotherapy) affects the efficacy through reshape the tumor microenvironment, which mainly includes different immune cells. Both traditional chemotherapy and chemoimmunotherapy own their pros and cons, which we list on the right of the figure. irAEs, immune-related adverse events.

As a kind of carcinoma with increasing morbidity, poor prognosis, and high mortality, esophageal squamous cell carcinoma (ESCC) is challenging for clinical management. Chemotherapy has been the standard treatment for ESCC over decades, while its clinical outcomes remain unsatisfying. And the regimen that combine standard chemotherapy with targeted therapy also demonstrates little effect. However, the advent of immune checkpoint inhibitors (ICI) proved to be a game changer in cancer treatment. Recent clinical trials had sprung up to evaluate the combined effect of ICI and chemotherapy regarding first-line ESCC treatment. What's more, researchers attempt to explore the possibility to implement ICI monotherapy regarding second-line ESCC treatment. In conclusion, most of the first-line trails present inspiring achievement, while ICI monotherapy indicates little improvement for ESCC treatment. To point out the heterogenicity that could be the potential reasons biasing the pooled results, the differences of PD-L1 immunohistochemistry (IHC) assays, geographic regions, chemotherapy regimens, and sex disparity among these trails are discussed respectively. In addition, the adverse events occurred during the trails are summarized, which confirm the safety of immunotherapy and chemoimmunotherapy. The article comprehensively reviews the representative explorations of using chemoimmunotherapy strategies in ESCC, as well as the deficiencies among them. Moreover, we highlight some feasible approaches. It will be beneficial for conducting more precise clinical trials on chemoimmunotherapy for ESCC in the future, including the use of more appropriate PD-L1 IHC assays, careful consideration of the heterogeneity of the enrolled population and the optimal combination of chemotherapy and ICI.

Article Access: https://doi.org/10.1002/mef2.56

More about MedComm-Future Medicine: https://onlinelibrary.wiley.com/journal/27696456

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