Dataset Information

Specific recognition of an FGFR2 fusion by tumor infiltrating lymphocytes from a patient with metastatic cholangiocarcinoma.

ABSTRACT:

Background

Metastatic cholangiocarcinoma (CC), a form of gastrointestinal cancer that originates from the bile ducts, cannot be cured by currently available therapies, and is associated with dismal prognosis. In a previous case report, adoptive transfer of autologous tumor infiltrating lymphocytes (TILs), the majority of which recognized a tumor-specific point mutation, led to a profound and durable cancer regression in a patient with metastatic CC. Thus, more effective treatment for patients with this disease may be developed by using TILs that target cancer-specific mutations, but also other genetic aberrations such as gene fusions. In this context, fusions that involve fibroblast growth factor receptor 2 (FGFR2) and function as oncogenes in a subset of patients with intrahepatic CC (ICC) represent particularly attractive targets for adoptive cell therapy. However, no study to date has explored whether FGFR2 fusions can be recognized by patients' T cells.

Method

To address whether FGFR2 fusions can be recognized by patients' T cells, we tested TILs from four patients with FGFR2 fusion-positive ICC for recognition of peptides and minigenes that represented the breakpoint regions of these fusions, which were unique to each of the four patients.

Results

We found that CD4⁺ TILs from one patient specifically recognized the breakpoint region of a unique FGFR2-TDRD1 (tudor domain-containing 1) fusion, and we isolated a T-cell receptor responsible for its recognition.

Conclusions

This finding suggests that FGFR2 fusion-reactive TILs can be isolated from some patients with metastatic ICC, and thus provides a rationale for future exploration of T cell-based therapy targeting FGFR2 fusions in patients with cancer. Furthermore, it augments the rationale for extending such efforts to other types of solid tumors hallmarked by oncogenic gene fusions.

SUBMITTER: White BS

PROVIDER: S-EPMC10106037 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature

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Publications

Specific recognition of an <i>FGFR2</i> fusion by tumor infiltrating lymphocytes from a patient with metastatic cholangiocarcinoma.

White Bradley Sinclair BS Sindiri Sivasish S Hill Victoria V Gasmi Billel B Nah Shirley S Gartner Jared J JJ Prickett Todd D TD Li Yong Y Gurusamy Devikala D Robbins Paul P Rosenberg Steven A SA Leko Vid V

Journal for immunotherapy of cancer 20230401 4

<h4>Background</h4>Metastatic cholangiocarcinoma (CC), a form of gastrointestinal cancer that originates from the bile ducts, cannot be cured by currently available therapies, and is associated with dismal prognosis. In a previous case report, adoptive transfer of autologous tumor infiltrating lymphocytes (TILs), the majority of which recognized a tumor-specific point mutation, led to a profound and durable cancer regression in a patient with metastatic CC. Thus, more effective treatment for pat ...[more]

PMID: 37045473

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