Cd70, also known as CD27L, is an immune checkpoint molecule. It binds to its receptor CD27, and under physiological conditions, their tightly controlled expression plays a role in co-stimulation in immune responses. The CD70-CD27 axis is involved in regulating immune cell activation and function, which is of great biological importance in the immune system [1].

In many hematological and solid malignancies, the CD70-CD27 axis is dysregulated. In hematological malignancies, cancer cells co-express CD70 and CD27, promoting stemness, proliferation, and survival of the malignancy [1]. In solid tumors like non-small cell lung cancer, CD70 is highly upregulated in epithelial-to-mesenchymal transition (EMT)-associated epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) resistance, and it promotes cell survival and invasiveness [2]. Nasopharyngeal carcinoma cells enhance the development and suppressive activity of regulatory T cells via the CD70-CD27 interaction, leading to immune evasion, and CD70 knockout inhibits a lipid signaling network in CD4+ naïve and regulatory T cells [3]. For acute myeloid leukemia, CD70 is expressed on most leukemic blasts but not on normal hematopoietic stem cells, and CD70-targeted CAR T-cell therapy shows anti-leukemia activity in preclinical models, though it didn't completely eliminate leukemia in vivo [5,6]. In clear cell renal cell carcinoma, CD70-targeted allogeneic CAR T-cell therapy shows favorable preclinical and clinical results [4]. Also, tandem CAR-T cells targeting CD70 and B7-H3 exhibit enhanced antitumor functionality against multiple solid tumors [7]. IL-15-secreting CAR natural killer cells directed toward CD70 can eliminate both cancer cells and cancer-associated fibroblasts in colorectal and pancreatic cancers [8]. CD70 CAR T cells secreting a bispecific T-cell engaging antibody molecule targeting CD33 can overcome AML antigen heterogeneity [9]. Allogeneic CAR T cells targeting CD70 for renal cell carcinoma show robust antitumor activity in preclinical models [10].

In conclusion, Cd70 plays a crucial role in the regulation of immune responses and is significantly involved in the development and progression of various malignancies. Studies using gene-targeting models, especially in the context of cancer, have revealed its role in promoting tumor cell survival, immune evasion, and resistance to therapy. These findings suggest that targeting Cd70 could be a promising strategy for treating related malignancies.