Both Th1 and Th2 CD4 + T-Cell Lineage Infiltrations Decrease in Post-hematopoietic Stem Cell Transplantation Colon Adenoma.

Abstract

Purpose: As long-term survival improves after allogeneic hematopoietic stem cell transplantation (HSCT), the risk for secondary solid cancers, including colon cancer, also increases. However, the pathogenesis of secondary solid cancers in post-HSCT patients remains unclear. This study aimed to investigate the involvement of local immunity in colon carcinogenesis in post-HSCT patients by assessing the infiltrating T cells in colon adenomas as premalignant lesions of colon cancer in adenoma-carcinoma sequence.

Methods: Colon adenoma samples obtained from 19 post-HSCT patients and 57 non-HSCT participants were analyzed via immunohistochemistry. Double staining of CD4/T-bet, CD4/GATA3, and CD4/FoxP3 was performed for evaluation of helper T-cell lineages (Th1, Th2, and regulatory T cells, respectively) and CD8 staining for CD8⁺ T cells.

Results: There were no significant between-group differences in the number of infiltrating CD4⁺ T cells and CD8⁺ T cells in adenomas. However, the number of both CD4⁺/T-bet⁺ and CD4⁺/GATA3⁺ T cells was significantly lower in the post-HSCT adenomas than in the non-HSCT adenomas (P = 0.0171 and 0.0009, respectively), whereas no significant differences were found in the number of CD4⁺/FoxP3⁺ cells.

Conclusion: Although the number of infiltrating CD4⁺ and CD8⁺ T cells, and even Treg cell counts, is sufficiently recovered post-HSCT, CD4⁺ T-cell dysfunction due to suppressed activation and differentiation in colon adenomas might be involved in colon carcinogenesis in post-HSCT patients. Elucidating the pathogenesis will contribute to the development of effective screening and prevention programs for secondary colon cancer in post-HSCT patients.