Kidney Week

Abstract: TH-PO1139

Transcriptionally Reprogrammed Circulating CD4 and CD8 T Cells in Post-Transplant Cancer

Session Information

• Onconephrology: Emerging Biomarkers, Preclinical Models, Clinical Challenges, and Therapeutic Strategies
  October 22, 2026 | Location: Exhibit Hall A, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Onconephrology

• 1600 Onconephrology

Authors

• Alfieri, Carlo, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Lombardy, Italy

Carlo Alfieri, MD

• Mattinzoli, Deborah, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Lombardy, Italy

Deborah Mattinzoli, PhD

• Ikehata, Masami, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Lombardy, Italy

Masami Ikehata, MD, PhD

• Armelloni, Silvia, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Lombardy, Italy

Silvia Armelloni, PhD

• Simeoni, Mariadelina, Universita degli Studi della Campania Luigi Vanvitelli, Caserta, Campania, Italy

Mariadelina Simeoni, MD, PhD, APN

• Mella, Alberto, Universita degli Studi di Torino, Turin, Piedmont, Italy

Alberto Mella

• Castellano, Giuseppe, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Lombardy, Italy

Giuseppe Castellano, MD, PhD

Background

Kidney transplant recipients (KTRs) have an increased cancer risk, partly related to chronic immunosuppression. This study investigates the transcriptional profiles of circulating CD4 and CD8 T cells to better define the molecular basis of impaired anti-tumor immunity after kidney transplantation.

Methods

PBMCs from two independent KTR cohorts (n=26), stratified by cancer status (CA+ or CA-), were analyzed. CD4 and CD8 T cells were FACS-sorted and subjected to RNA-seq. Differential expression was assessed with DESeq2, followed by gene ontology and pathway enrichment analyses. After filtering, 16,102 CD4 and 16,033 CD8 genes were retained.

Results

In CA+ KTRs, CD4 T cells showed loss of helper and proliferative programs (e.g., CDC20, BIRC5), with upregulation of innate/myeloid-like markers (STAB1, CLEC4A), pro-inflammatory genes (IL1B, PTGS2), tissue-remodelling and angiogenic pathways (VCAN, PDGFRB), and metabolic/stress-adaptation regulators (G0S2, FADS1, FOXK2, POU2F1, APOL1). Residual cytotoxic transcripts were still detectable, but likely ineffective. CD8 T cells showed downregulation of cytotoxic and migratory genes (BIRC7, CCR6, HLA-B) and upregulation of stress-response, metabolic, adhesion, and extracellular matrix-related genes (NXPH4, ULBP2, PYDC5, MT-ND4L, FGF22) (Fig 1). They remained metabolically and transcriptionally active despite reduced cytotoxic potential. The validation cohort reproduced these findings, with partially overlapping genes but consistent functional signatures, supporting robust transcriptional reprogramming (Fig 2). Both T-cell populations adopted programs favouring a cancer-permissive environment.

Conclusion

In KTRs with cancer, circulating CD4 and CD8 T cells show transcriptional reprogramming, lose key anti-tumor functions, and promote a cancer-permissive environment. These findings define the basis of T-cell dysfunction in post-transplant malignancy and highlight targets for restoring anti-tumor immunity.

Funding

• Government Support – Non-U.S.