Journal for immunotherapy of cancer · 2026
Correlation between recognition of autologous tumor organoids by tumor-infiltrating lymphocytes from metastatic epithelial cancers and clinical response.
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Gustafson Alexandra M, Bhasin Aarushi, Gasmi Billel, Bui Brian D, Ade Catherine Marie, Hanada Ken-Ichi, Halas Hyunmi K, Gartner Jared J, Prickett Todd D, Salazar Jon, Parkhust Maria R, Robbins Paul, Klemen Nicholas D, Kwong Mei Li, Goff Stephanie L, Rosenberg Steven A, Yang James C
Аннотация
BACKGROUND: Neoantigen-specific tumor-infiltrating lymphocytes (TILs) have the ability to mediate responses in patients with metastatic epithelial cancers. While some identified factors are associated with response, there is a need for ways to determine which patients will benefit from adoptive cell therapy with TIL. Patient-derived tumor organoids (PDTO) retain the genetic makeup of the tumor from which they are derived, and are a useful tool in personalized medicine to test the effectiveness of anticancer therapies.
METHODS: Tumor organoids were grown from patients with metastatic epithelial cancers treated on a TIL protocol. TIL recognition of autologous PDTO by enzyme-linked immunosorbent spot assays and 4-1BB upregulation, as well as objective Response Evaluation Criteria in Solid Tumors (RECIST) responses to treatment, were measured in a cohort of treated patients. The most common histologies were colorectal (20 patients, 67%), pancreatic (4 patients, 13%), and breast (2 patients, 7%) cancer.
RESULTS: Recognition of PDTO was driven by major histocompatibility complex (MHC) class I-restricted reactivity and upregulation of MHC in response to interferon-γ was not associated with response. There were no responders in the 9 patients who lacked PDTO recognition on their initial TIL screening compared with seven responses in 18 patients with initial reactivity (p=0.059). After TIL were selected and expanded for administration, 15 infusion products showed organoid recognition, with 8 of these patients achieving objective responses (53%), while only 1 of 15 patients without organoid recognition responded (7%; p=0.014).
CONCLUSIONS: TIL reactivity against autologous tumor organoid appears to be associated with objective clinical response in patients with metastatic epithelial cancers.
METHODS: Tumor organoids were grown from patients with metastatic epithelial cancers treated on a TIL protocol. TIL recognition of autologous PDTO by enzyme-linked immunosorbent spot assays and 4-1BB upregulation, as well as objective Response Evaluation Criteria in Solid Tumors (RECIST) responses to treatment, were measured in a cohort of treated patients. The most common histologies were colorectal (20 patients, 67%), pancreatic (4 patients, 13%), and breast (2 patients, 7%) cancer.
RESULTS: Recognition of PDTO was driven by major histocompatibility complex (MHC) class I-restricted reactivity and upregulation of MHC in response to interferon-γ was not associated with response. There were no responders in the 9 patients who lacked PDTO recognition on their initial TIL screening compared with seven responses in 18 patients with initial reactivity (p=0.059). After TIL were selected and expanded for administration, 15 infusion products showed organoid recognition, with 8 of these patients achieving objective responses (53%), while only 1 of 15 patients without organoid recognition responded (7%; p=0.014).
CONCLUSIONS: TIL reactivity against autologous tumor organoid appears to be associated with objective clinical response in patients with metastatic epithelial cancers.