To evaluate the role of HHLA2 in colorectal cancer, we assessed its levels in relation to various parameters, including MSI status, CD8+ cells, and the histopathological features such as budding, tumor-infiltrating lymphocytes (TILs), the response of the host immune system, TNM scale, grading, cytokines, chemokines, and cell signaling molecule panels. Here, HHLA2 is linked to neoplasm.