**Abstract**

Extracellular vesicles (EVs), like exosomes and microvesicles, are membrane-bound vesicles released by most cell types in response to cellular stress as well as normal physiologic conditions. EV plays a vital part in cell communication and tumor immunology. Tumor-derived EVs carry a wide range of tumor neoantigens and have a distinct molecular signature that reflects the tumor's genomic complexities. These tumorderived EVs provide a glance into the immunological tumor microenvironment and have a perspective to be a novel, minimally invasive cancer immunotherapy biomarker. Antibodies against immune checkpoint inhibitors like anti-programmed death-1 (PD-1) and its ligand (PD-L1) have changed the treatment of broad diversity of solid tumors such as non-small cell lung cancer, head, and neck squamous cell carcinoma, urothelial carcinoma, melanoma, etc. Invasive tissue biopsy is necessary for both histologic diagnosis and next-generation sequencing efforts. The latter has become increasingly widespread in today's healthcare. There is an unmet need for non-invasive or minimally invasive (e.g., plasma-based) biomarkers in both diagnosis and therapy monitoring. The selected investigation of EV in biospecimens, including plasma and saliva, can achieve this goal by potentially avoiding the need for tissue samples. In this chapter, we discuss the present challenges of biomarkers in cancer immunotherapy and the mechanistic role of tumor-derived EV in regulating the anti-tumor immune response.

**Keywords:** extracellular vesicles, cancer, immune response, biomarkers, immunotherapy
