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Background <p>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.</p> Methods <p>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)<b>.</b></p> Results <p>Tfh and Tfc cells were significantly increased in peripheral blood of CRC patients compared with controls (<i>p</i> &lt; 0.001 and <i>p</i> = 0.006, respectively). Their frequencies were higher in tumor-infiltrating lymphocytes (TILs) than in normal colonic tissue (<i>p</i> = 0.002 and <i>p</i> &lt; 0.001) and peripheral blood (<i>p</i> &lt; 0.001). Their ICOS expression was significantly elevated in patients’ blood (<i>p</i> = 0.008 and <i>p</i> = 0.04) and highest in TIL (<i>p</i> = 0.02) compared to the normal tissue and peripheral blood of patients (<i>p</i> &lt; 0.001). TIGIT⁺VISTA⁺ follicular T-cell subsets were significantly expanded in the peripheral blood of patients, with peak expression in TILs (<i>p</i> &lt; 0.001).</p> Conclusions <p>Follicular T cells are enriched and highly activated in CRC, particularly within the tumor microenvironment. The predominance of TIGIT<sup>+</sup> VISTA<sup>+</sup> subsets suggests a dual role in antitumor immunity and immune escape. These cells serve as biomarkers and potential targets for immunotherapy.</p>

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

  • 期刊论文

  • 发表日期：

    2026年7月8日

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  • Asmaa M. Zahran,
  • Nahla M. Elsherbiny,
  • Alshimaa G. Abdelhakeem,
  • Amal Rayan,
  • Zainab Gaber Mahran,
  • Ahmed Khalid Ibrahim Elsayh,
  • Emad Saad,
  • Ahmed Refaat,
  • Radwan Abdelsabour,
  • Doaa A. Gamal,
  • Wageeh A. Ali,
  • Zeinab Albadry M. Zahran,
  • Hossam Elashmawy,
  • Shimaa Gafar Mansor

摘要

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.