Revealing the dynamics of follicular T cells and checkpoint engagement in surgically resected colorectal cancer and their relations to clinicopathological aspects.

BACKGROUND

Follicular T cells contribute to B-cell responses and antitumor immunity, yet their immune checkpoint expression and role in colorectal cancer (CRC) remain insufficiently characterized. We evaluated the distribution, activation status, and checkpoint expression of follicular helper and follicular cytotoxic T-cell subsets (Tfh and Tfc) in CRC patients and their association with clinicopathological features.

METHODS

Thirty-three CRC patients and 25 healthy controls were recruited from South Egypt Cancer Institute, Assiut University. Flow cytometry was used to assess follicular T-cell subsets and their expression of inducible T-cell costimulatory (ICOS), T-cell immunoreceptor with Ig and ITIM domains (TIGIT) and V-domain Ig Suppressor of T-cell Activation (VISTA).

RESULTS

Tfh and Tfc cells were significantly increased in peripheral blood of CRC patients compared with controls (p < 0.001 and p = 0.006, respectively). Their frequencies were higher in tumor-infiltrating lymphocytes (TILs) than in normal colonic tissue (p = 0.002 and p < 0.001) and peripheral blood (p < 0.001). Their ICOS expression was significantly elevated in patients' blood (p = 0.008 and p = 0.04) and highest in TIL (p = 0.02) compared to the normal tissue and peripheral blood of patients (p < 0.001). TIGIT⁺VISTA⁺ follicular T-cell subsets were significantly expanded in the peripheral blood of patients, with peak expression in TILs (p < 0.001).

CONCLUSIONS

Follicular T cells are enriched and highly activated in CRC, particularly within the tumor microenvironment. The predominance of TIGIT+ VISTA+ subsets suggests a dual role in antitumor immunity and immune escape. These cells serve as biomarkers and potential targets for immunotherapy.