Cholangiocarcinoma (CCA) is a rare and aggressive malignancy originating from the bile ducts, with poor prognosis and limited treatment options. Traditional therapies, such as surgery, chemotherapy, and radiation, have shown limited efficacy, especially in advanced cases. Recent advancements in immunotherapy, particularly T cell-based therapies like chimeric antigen receptor T (CAR T) cells, tumor-infiltrating lymphocytes (TILs), and T cell receptor (TCR)-based therapies, have opened new avenues for improving outcomes in CCA. This review provides a comprehensive overview of the current state of T cell therapies for CCA, focusing on CAR T cell therapy. It highlights key challenges, including the complex tumor microenvironment and immune evasion mechanisms, and the progress made in preclinical and clinical trials. The review also discusses ongoing clinical trials targeting specific CCA antigens, such as MUC1, EGFR, and CD133, and the evolving role of precision immunotherapy in enhancing treatment outcomes. Despite significant progress, further research is needed to optimize these therapies for solid tumors like CCA. By summarizing the most recent clinical results and future directions, this review underscores the promising potential of T cell therapies in revolutionizing CCA treatment.

Aims: Congenital and cyclical neutropenia are rare inherited diseases that result in recurrent life-threatening bacterial infections due to a deficiency of mature neutrophils. Cyclical neutropenia is usually caused by heterozygous ELANE mutations while congenital neutropenia is genetically heterogeneous with mutations in genes like ELANE, HAX-1, G6PC3 and GFI1. The presence of ELANE mutation aids in the establishment of diagnosis and rules out other secondary causes of neutropenia such as autoimmune cytopenia and evolving aplasia. Further, patients with ELANE mutations are also at a high risk of developing myelodysplasia or acute myeloid leukaemia. Hence it is important to screen for these mutations in patients presenting with neutropenia early in life. Methods: The study included 52 patients who were evaluated for inherited neutropenia. Genomic DNA was extracted from peripheral blood leucocytes and mutation analysis was done by bidirectional Sanger sequencing. Results: Ten different missense, frameshift or splice site variants in ELANE gene were identified in 11 patients: c.125C>T (p.Pro42Leu), c.164G>A (p.Cys55Tyr), c.169G>A (p.Ala57Thr), c.179T>C (p.Ile60Thr), c.770C>T (p.Pro257Leu), c.367–8C>A, c.597+1G>A along with three novel mutations c.302T>A (p.Val101Glu), c.468G>T (p.Try156Cys) and c.596delT (Phe199Ser fs*13). Family studies were available for three patients and, in all three instances, the mutation had a de novo origin. Conclusion: The widespread distribution of mutations suggests the need to screen all the exons in ELANE gene for proper characterisation of the genotype.