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Case Reports
. 2025 Feb 6;392(6):577-583.
doi: 10.1056/NEJMoa2411507.

CD4+ T-Cell Lymphoma Harboring a Chimeric Antigen Receptor Integration in TP53

Karlo Perica  1   2 , Nayan Jain  2 , Michael Scordo  1   3   4 , Ruchi Patel  5 , Ozgur Can Eren  6 , Utsav Patel  7 , Gunes Gundem  8 , Dylan Domenico  8 , Sneha Mitra  9 , Nicholas D Socci  5 , John K Everett  10 , Aoife M Roche  10 , Angelina Petrichenko  10 , Gunjan L Shah  1   3   4 , Maria E Arcila  7 , Laetitia Borsu  7 , Jae H Park  1   4   11 , Steven M Horwitz  1   4   12 , Sergio A Giralt  1   3   4 , Ahmet Dogan  6 , Christina Leslie  9 , Elli Papaemmanuil  8 , Frederic D Bushman  10 , Saad Z Usmani  1   3   4   13 , Michel Sadelain  2 , Sham Mailankody  1   4   13
Affiliations
Case Reports

CD4+ T-Cell Lymphoma Harboring a Chimeric Antigen Receptor Integration in TP53

Karlo Perica et al. N Engl J Med. .

Abstract

Malignant T-cell transformation after chimeric antigen receptor (CAR) T-cell therapy has been described, but the contribution of CAR integration to oncogenesis is not clear. Here we report a case of a T-cell lymphoma harboring a lentiviral integration in a known tumor suppressor, TP53, which developed in a patient with multiple myeloma after B-cell maturation antigen (BCMA) CAR T-cell therapy.

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Figures

Figure 1.
Figure 1.. Pathological staining from the duodenal biopsy.
A) Dense lymphocytic infiltrate that is B) CD4 positive by immunohistochemistry. C) p53 staining shows dim or absent expression in T cell infiltrate; low power with inset. E-F) Phosphorylated STAT3 (pSTAT3) IHC showed positive staining.
Figure 1.
Figure 1.. Pathological staining from the duodenal biopsy.
A) Dense lymphocytic infiltrate that is B) CD4 positive by immunohistochemistry. C) p53 staining shows dim or absent expression in T cell infiltrate; low power with inset. E-F) Phosphorylated STAT3 (pSTAT3) IHC showed positive staining.
Figure 1.
Figure 1.. Pathological staining from the duodenal biopsy.
A) Dense lymphocytic infiltrate that is B) CD4 positive by immunohistochemistry. C) p53 staining shows dim or absent expression in T cell infiltrate; low power with inset. E-F) Phosphorylated STAT3 (pSTAT3) IHC showed positive staining.
Figure 1.
Figure 1.. Pathological staining from the duodenal biopsy.
A) Dense lymphocytic infiltrate that is B) CD4 positive by immunohistochemistry. C) p53 staining shows dim or absent expression in T cell infiltrate; low power with inset. E-F) Phosphorylated STAT3 (pSTAT3) IHC showed positive staining.
Figure 1.
Figure 1.. Pathological staining from the duodenal biopsy.
A) Dense lymphocytic infiltrate that is B) CD4 positive by immunohistochemistry. C) p53 staining shows dim or absent expression in T cell infiltrate; low power with inset. E-F) Phosphorylated STAT3 (pSTAT3) IHC showed positive staining.
Figure 2.
Figure 2.. Molecular studies from the duodenal biopsy and peripheral blood.
A. Frequency TCR clones by VDJ immunosequencing in peripheral blood and duodenal biopsy at indicated days post CAR T cell infusion. Selected clones are among the ten most abundant in at least one timepoint. The most abundant clonotype in the duodenal biopsy is highlighted in red. 2B. Frequency of CAR integration sites in the duodenal biopsy sample. Cell clone sizes associated with unique integration sites are quantified using the SonicAbundance method. * Indicates an integration site within a gene; ~ indicates an annotated cancer-associated gene. Numbers below gene names indicate chromosome and chromosomal positions. LowAbund indicates pooled low abundance integration sites. C. Variant allele frequency (VAF) of indicated DNTM3a and SOCS1 mutations in peripheral blood and duodenal biopsy at indicated days post CAR T cell infusion; peripheral blood sample results are from whole genome sequencing and the duodenal biopsy from whole exome sequencing. D. Single cell RNA expression dot plots of mean expression and frequency of indicated genes (x axis) by leiden cluster (y axis).
Figure 2.
Figure 2.. Molecular studies from the duodenal biopsy and peripheral blood.
A. Frequency TCR clones by VDJ immunosequencing in peripheral blood and duodenal biopsy at indicated days post CAR T cell infusion. Selected clones are among the ten most abundant in at least one timepoint. The most abundant clonotype in the duodenal biopsy is highlighted in red. 2B. Frequency of CAR integration sites in the duodenal biopsy sample. Cell clone sizes associated with unique integration sites are quantified using the SonicAbundance method. * Indicates an integration site within a gene; ~ indicates an annotated cancer-associated gene. Numbers below gene names indicate chromosome and chromosomal positions. LowAbund indicates pooled low abundance integration sites. C. Variant allele frequency (VAF) of indicated DNTM3a and SOCS1 mutations in peripheral blood and duodenal biopsy at indicated days post CAR T cell infusion; peripheral blood sample results are from whole genome sequencing and the duodenal biopsy from whole exome sequencing. D. Single cell RNA expression dot plots of mean expression and frequency of indicated genes (x axis) by leiden cluster (y axis).
Figure 2.
Figure 2.. Molecular studies from the duodenal biopsy and peripheral blood.
A. Frequency TCR clones by VDJ immunosequencing in peripheral blood and duodenal biopsy at indicated days post CAR T cell infusion. Selected clones are among the ten most abundant in at least one timepoint. The most abundant clonotype in the duodenal biopsy is highlighted in red. 2B. Frequency of CAR integration sites in the duodenal biopsy sample. Cell clone sizes associated with unique integration sites are quantified using the SonicAbundance method. * Indicates an integration site within a gene; ~ indicates an annotated cancer-associated gene. Numbers below gene names indicate chromosome and chromosomal positions. LowAbund indicates pooled low abundance integration sites. C. Variant allele frequency (VAF) of indicated DNTM3a and SOCS1 mutations in peripheral blood and duodenal biopsy at indicated days post CAR T cell infusion; peripheral blood sample results are from whole genome sequencing and the duodenal biopsy from whole exome sequencing. D. Single cell RNA expression dot plots of mean expression and frequency of indicated genes (x axis) by leiden cluster (y axis).
Figure 2.
Figure 2.. Molecular studies from the duodenal biopsy and peripheral blood.
A. Frequency TCR clones by VDJ immunosequencing in peripheral blood and duodenal biopsy at indicated days post CAR T cell infusion. Selected clones are among the ten most abundant in at least one timepoint. The most abundant clonotype in the duodenal biopsy is highlighted in red. 2B. Frequency of CAR integration sites in the duodenal biopsy sample. Cell clone sizes associated with unique integration sites are quantified using the SonicAbundance method. * Indicates an integration site within a gene; ~ indicates an annotated cancer-associated gene. Numbers below gene names indicate chromosome and chromosomal positions. LowAbund indicates pooled low abundance integration sites. C. Variant allele frequency (VAF) of indicated DNTM3a and SOCS1 mutations in peripheral blood and duodenal biopsy at indicated days post CAR T cell infusion; peripheral blood sample results are from whole genome sequencing and the duodenal biopsy from whole exome sequencing. D. Single cell RNA expression dot plots of mean expression and frequency of indicated genes (x axis) by leiden cluster (y axis).
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References

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