In vitro and in vivo experimental models for cancer immunotherapy study

Cancer incidence and mortality are increasing globally. Cancer immunotherapies, such as immune checkpoint inhibitors and adoptive cell therapy, have been recognized as a revolutionary treatment approach to combat cancer. However, immunotherapeutic resistance and cancer recurrence after immunotherapy alarm us to further explore the underlying mechanisms and develop new immunotherapies. Experimental models hold great value in cancer research studies such as deciphering the mechanism of tumor initiation and growth, drug discovery, and evaluation of immunotherapy efficacy. The ideal model is expected to recapitulate and mimic the human tumor microenvironment, including biological, physiological, and immunologic functionality. However, each model has its pros and cons, and the selection of a model depends on many factors, such as model features, study aims, and availability of related resources. In this review, we discussed commonly used models currently used in cancer research and immunotherapy, including 2D and 3D in vitro cell culture models such as spheroid, organoid, hydrogel model, and microfluidic chip, and in vivo mouse tumor models such as genetically engineered models, chemically induced models, cell-derived xenograft (CDX) models, patient-derived xenograft (PDX) models, and humanized mouse models. Both in vitro and in vivo preclinical models are powerful tools for studying cancer immunotherapy, but all these models have their limitations. To promote the success of clinical treatment in cancer therapy, advanced model systems that can better recapitulate the human tumor environment and host immune response are preferable options for preclinical study.