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Updated: Jan 5, 2026
Analysis of Human T Cell Activity in an Allogeneic Co-Culture Setting of Pre-Treated Tumor Cells
Published on: March 7, 2025
Polyfunctional tumor-reactive T cells are effectively expanded from non-small cell lung cancers, and correlate with
Rosa De Groot1,2, Marleen M Van Loenen1,3, Aurélie Guislain1,2
1Department of Hematopoiesis, Sanquin Research, Amsterdam, The Netherlands.
Abstract:
Non-small cell lung cancer (NSCLC) is the second most prevalent type of cancer. With the current treatment regimens, the mortality rate remains high. Therefore, better therapeutic approaches are necessary. NSCLCs generally possess many genetic mutations and are well infiltrated by T cells (TIL), making TIL therapy an attractive option. Here we show that T cells from treatment naive, stage I-IVa NSCLC tumors can effectively be isolated and expanded, with similar efficiency as from normal lung tissue. Importantly, 76% (13/17) of tested TIL products isolated from NSCLC lesions exhibited clear reactivity against primary tumor digests, with 0.5%-30% of T cells producing the inflammatory cytokine Interferon (IFN)-γ. Both CD4+ and CD8+ T cells displayed tumor reactivity. The cytokine production correlated well with CD137 and CD40L expression. Furthermore, almost half (7/17) of the TIL products contained polyfunctional T cells that produced Tumor Necrosis Factor (TNF)-α and/or IL-2 in addition to IFN-γ, a hallmark of effective immune responses. Tumor-reactivity in the TIL products correlated with high percentages of CD103+CD69+CD8+ T cell infiltrates in the tumor lesions, with PD-1hiCD4+ T cells, and with FoxP3+CD25+CD4+ regulatory T cell infiltrates, suggesting that the composition of T cell infiltrates may predict the level of tumor reactivity. In conclusion, the effective generation of tumor-reactive and polyfunctional TIL products implies that TIL therapy will be a successful treatment regimen for NSCLC patients.
Insights
Tumor-infiltrating lymphocyte (TIL) therapy shows promise for non-small cell lung cancer (NSCLC). Researchers successfully isolated and expanded tumor-reactive T cells from NSCLC patients, indicating TIL therapy
Area of Science:
- Immunology
- Oncology
- Cell Therapy
Background:
- Non-small cell lung cancer (NSCLC) has a high mortality rate despite current treatments.
- NSCLC tumors are often infiltrated by T cells, making tumor-infiltrating lymphocyte (TIL) therapy a potential treatment strategy.
- Existing therapeutic approaches for NSCLC require enhancement due to persistent high mortality rates.
Purpose of the Study:
- To investigate the feasibility and effectiveness of isolating and expanding tumor-infiltrating lymphocytes (TILs) from NSCLC tumors for therapeutic purposes.
- To assess the tumor reactivity and polyfunctionality of TILs derived from NSCLC patients.
- To explore potential correlations between TIL product characteristics and the composition of T cell infiltrates within NSCLC lesions.
Main Methods:
- Isolation and expansion of T cells from treatment-naive NSCLC tumors (Stages I-IVa) and normal lung tissue.
- Assessment of TIL product reactivity against primary tumor digests using cytokine production assays (e.g., Interferon-gamma).
- Flow cytometry analysis to characterize T cell populations (CD4+, CD8+, polyfunctional T cells) and tumor infiltrates (CD103, CD69, PD-1, FoxP3, CD25).
Main Results:
- T cells were effectively isolated and expanded from NSCLC tumors with similar efficiency to normal lung tissue.
- 76% of tested TIL products demonstrated significant tumor reactivity, with T cells producing inflammatory cytokines like Interferon-gamma (IFN-γ).
- Nearly half of the TIL products contained polyfunctional T cells (producing TNF-α and/or IL-2 alongside IFN-γ), and tumor reactivity correlated with specific T cell infiltrate profiles.
Conclusions:
- Effective generation of tumor-reactive and polyfunctional TIL products is achievable from NSCLC patients.
- TIL therapy holds significant potential as a successful treatment regimen for non-small cell lung cancer.
- The composition of T cell infiltrates within tumors may serve as a predictive marker for TIL product efficacy.
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