Immune checkpoint molecules such as PD-1 and cytotoxic T-lymphocyte antigen 4 (CTLA-4) are typically used to inhibit T cell activity, and the ECM in the tumor microenvironment may enhance the expression of PD-1 on T cell surfaces by interacting with cell surface receptors such as integrins and CD44, thereby promoting tumor immune escape (89, 90). Here, CD44 is linked to neoplasm.