Emerging Immune Checkpoint Molecules on Cancer Cells: CD24 and CD200

Abstract

Cancer immunotherapy strategies are based on the utilization of immune checkpoint inhibitors to instigate an antitumor immune response. The efficacy of immune checkpoint blockade, directed at adaptive immune checkpoints, has been demonstrated in select cancer types. However, only a limited subset of patients has exhibited definitive outcomes characterized by a sustained response after discontinuation of therapy. Recent investigations have highlighted the significance of immune checkpoint molecules that are overexpressed in cancer cells and inhibit myeloid lineage immune cells within a tumor microenvironment. These checkpoints are identified as potential targets for anticancer immune responses. Notably, the immune checkpoint molecules CD24 and CD200 have garnered attention owing to their involvement in tumor immune evasion. CD24 and CD200 are overexpressed across diverse cancer types and serve as signaling checkpoints by engaging their respective receptors, Siglec-10 and CD200 receptor, which are expressed on tumor-associated myeloid cells. In this review, we summarized and discussed the latest advancements and insights into CD24 and CD200 as emergent immune checkpoint moieties, further delving into their therapeutic potentials for cancer treatment.

Translation of Data from Animal Models of Cancer to Immunotherapy of Breast Cancer and Chronic Lymphocytic Leukemia

“…Where relevant, similar research by other groups, again using animal studies, have been cited, both in support of, and occasionally contradictory to, our own findings. No significant review of the growing body of clinical literature available, which supports many of these observations, has been attempted, but the interested reader is referred to the following references as an introduction to this rapidly growing field [ 16 , 103 , 104 , 105 , 106 , 107 ]. There can be little doubt that ongoing use of animal models will in the future, as in the past, drive expansion of this vast area of translational research.…”

From mechanism to therapy: the journey of CD24 in cancer

“…CD24 is emerging as a pivotal modulator in the immune evasion mechanisms of cancer cells, acting as a novel phagocytosis checkpoint that manipulates the immune system to recognize and eliminate malignant cells (8,56,144). Through its interaction with the inhibitory receptor Siglec-10 on macrophages, CD24 effectively sends a "don't eat me" signal, thereby preventing the phagocytosis of cancer cells (49).…”

“…CD24 has been found to be overexpressed in a variety of cancers, including B-cell lymphomas, cholangiocarcinoma, pancreatic adenocarcinoma, urothelial carcinoma, erythroleukemia, gliomas, breast cancer, small cell lung cancer, esophageal squamous cell carcinoma, hepatocellular carcinoma, ovarian cancer, primary neuroendocrine carcinomas and prostate carcinomas (8,148,(215)(216)(217)(218)(219)(220)(221)(222)(223)(224)(225)(226)(227)(228)(229). Its overexpression has been shown to increase the adhesion of cancer cells to extracellular matrix proteins, such as laminin and collagen, and to promote cell migration and invasion.…”

“…Most of the immunotherapies developed in the past primarily aimed at stimulating adaptive immunity, especially by reinvigorating and enhancing T cell responses. However, recent research has revealed that innate immune checkpoints expressed on antigen-presenting cells (APCs) play a pivotal role in immune evasion (8)(9)(10). Some checkpoints are responsible for detecting and eliminating cancer cells through phagocytosis while also restraining the innate immune response (11,12).…”

Checkpoint CD24 function on tumor and immunotherapy

“…This interaction promotes immune escape of tumor cells and creates a new immune checkpoint in the form of a “don’t eat me” signal ( 7 , 8 ). Therefore, CD24 has become a potential therapeutic target for cancer treatments, including antibody drugs, gene therapy, chimeric antigen receptor (CAR) T cell therapy, and more ( 9 , 10 ). In addition, anti-tumor therapy targeting CD24 can also affect the tumor microenvironment and promote the immune system’s attack on the tumor, so CD24 may also be a target for immunotherapy ( 11 ).…”