Cd70, also known as CD70 antigen, is an immune checkpoint molecule. Its tightly controlled expression under physiological conditions plays a role in co-stimulation in immune responses. It interacts with its receptor CD27, and the CD70-CD27 axis is involved in multiple biological processes related to the immune system [1].

The CD70-CD27 axis is aberrantly expressed in many hematological and solid malignancies. In hematological malignancies, cancer cells co-express CD70 and CD27, promoting stemness, proliferation, and survival of malignancy. In solid tumors, CD70 expression on tumor cells can facilitate immune evasion through CD27 expression in the tumor microenvironment [1]. In non-small cell lung cancer, CD70 is highly upregulated in EMT-associated resistance to EGFR tyrosine kinase inhibitors, promoting cell survival and invasiveness [2]. Nasopharyngeal carcinoma cells enhance the development and suppressive activity of regulatory T cells via CD70-CD27 interaction, and CD70 blocking can reinvigorate CD8+ T-cell immunity [3]. CD70-targeted allogeneic CAR T-cell therapy shows potential for advanced clear cell renal cell carcinoma [4]. Anti-CD70 CAR-T cells are a potential treatment for acute myeloid leukemia, though they did not completely eliminate leukemia in vivo [5]. Tandem CAR-T cells targeting CD70 and B7-H3 exhibit enhanced antitumor functionality against multiple solid tumors [6]. IL-15-secreting CAR natural killer cells directed toward CD70 can eliminate both cancer cells and cancer-associated fibroblasts [7]. CD70 CAR T cells secreting a bispecific T-cell engaging antibody targeting CD33 can overcome antigen heterogeneity in AML [8]. Anti-CD70 allogeneic CAR T cells targeting renal cell carcinoma show efficacy and safety in pre-clinical studies [9].

In conclusion, Cd70, through its interaction with CD27, is crucial in the dysregulation of the tumor microenvironment in various malignancies. Studies using different models, such as CAR-T cell-based approaches which can be considered as functional knockdown models in a sense, have revealed its role in promoting tumor progression and immunosuppression. These findings highlight Cd70 as a potential therapeutic target in oncology.