Therapeutic targets and biomarkers of tumor immunotherapy: response versus non-response

Abstract

Cancers are highly complex diseases that are characterized by not only the overgrowth of malignant cells but also an altered immune response. The inhibition and reprogramming of the immune system play critical roles in tumor initiation and progression. Immunotherapy aims to reactivate antitumor immune cells and overcome the immune escape mechanisms of tumors. Represented by immune checkpoint blockade and adoptive cell transfer, tumor immunotherapy has seen tremendous success in the clinic, with the capability to induce long-term regression of some tumors that are refractory to all other treatments. Among them, immune checkpoint blocking therapy, represented by PD-1/PD-L1 inhibitors (nivolumab) and CTLA-4 inhibitors (ipilimumab), has shown encouraging therapeutic effects in the treatment of various malignant tumors, such as non-small cell lung cancer (NSCLC) and melanoma. In addition, with the advent of CAR-T, CAR-M and other novel immunotherapy methods, immunotherapy has entered a new era. At present, evidence indicates that the combination of multiple immunotherapy methods may be one way to improve the therapeutic effect. However, the overall clinical response rate of tumor immunotherapy still needs improvement, which warrants the development of novel therapeutic designs as well as the discovery of biomarkers that can guide the prescription of these agents. Learning from the past success and failure of both clinical and basic research is critical for the rational design of studies in the future. In this article, we describe the efforts to manipulate the immune system against cancer and discuss different targets and cell types that can be exploited to promote the antitumor immune response.

Another Brick to Confirm the Efficacy of Rigosertib as Anticancer Agent

“…Moreover, targeted therapy could be an option for treating lung NSCLS. For example, tyrosine kinase inhibitors (Gefitinib and Erlotinib) or ALK inhibitors (Crizotinib and Alectinib) can be used to treat patients with EGFR (10–15%) and ALK (3–7%) gene mutations, respectively [ 28 , 29 , 30 , 31 ]; monoclonal antibodies against PD-1 (Nivolumab) and PD-L1 (Atezolizumab) are used as immune checkpoints inhibitors and they have greatly improved the chance of treatment success of NSCLC in recent years [ 32 , 33 , 34 ].…”

“…However, these treatments frequently present debilitating side effects (diarrhea, pulmonary inflammation, polyneuropathies, cytopenia, and nephrotoxicity) which require a dose reduction or total interruption of the treatment [ 27 , 32 ]. Furthermore, tyrosine kinase and ALK inhibitors may not be effective in all patients.…”

“…Glioblastoma is the most frequent brain neoplasm. It has a very rapid course and, due to late diagnosis and lack of effective therapies, its mortality rate is very high [ 31 , 32 ]. The first-line treatment in this type of tumor is surgical resection, although it can often be followed by radiotherapy and chemotherapy.…”

“…The latter currently offers few effective options, among which temozolomide and nitrosoureas are the most used. This lack of chemotherapy options is mainly due to the high heterogeneity of the tumor, the abundance of cancer stem cells, the high drug resistance, and the difficulty of crossing the blood–brain barrier for many anticancer drugs [ 32 ].…”

Mannosylated-Serum Albumin Nanoparticle Imaging to Monitor Tumor-Associated Macrophages under Anti- PD1 Treatment

“…Because of the spatial and temporal heterogeneity of tumor microenvironment, biomarkers based on tissue samples have limitations in the representativeness of whole metastatic tumors [48]. For example, PD-L1 expression measured by immunohistochemistry, the most commonly used biomarker for immune checkpoint inhibitors, is commonly assessed by archive tissue samples for patients with metastatic tumors [49]. The temporal changes of tumor immune status mediated by several treatment before the immune-oncologic drugs is hard to be re ected by this archived samples.…”