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T cells expanded from renal cell carcinoma display tumor-specific CD137 expression but lack significant IFN-γ, TNF-α

Saskia D van Asten1,2, Rosa de Groot2,3,4, Marleen M van Loenen2,3

  • 1Department of Immunopathology, Sanquin Research, Amsterdam, The Netherlands.

Oncoimmunology
|February 4, 2021
PubMed

Insights

Tumor-infiltrating lymphocytes (TILs) from metastatic renal cell carcinoma (RCC) lesions show tumor reactivity. However, these TILs exhibit limited cytokine production against autologous tumors, necessitating further research into immunosuppressive factors for improved TIL therapy in RCC patients.

Area of Science:

  • Oncology
  • Immunology
  • Cancer Research

Background:

  • Metastatic renal cell carcinoma (RCC) has a poor prognosis, with limited response to current immune checkpoint inhibitors.
  • Autologous tumor-infiltrating lymphocyte (TIL) therapy presents a potential alternative for patients refractory to anti-PD-1 therapy.

Purpose of the Study:

  • To assess the tumor reactivity and cytokine production of TILs from RCC lesions.
  • To correlate TIL reactivity with immune cell composition within tumor lesions.
  • To investigate the potential of TIL therapy in advanced RCC.

Main Methods:

  • Comparison of immune infiltrate composition between RCC lesions and autologous kidney tissue from 18 patients.
  • Generation and expansion of TIL products from RCC lesions.
  • Assessment of TIL tumor reactivity via CD137 upregulation upon exposure to autologous tumor digests.
  • Analysis of cytokine production (IFN-γ, TNF-α, IL-2) by TILs in response to autologous tumors.

Main Results:

  • Increased T cell infiltrates, predominantly CD8+ effector memory T cells, were observed in RCC lesions compared to normal kidney tissue.
  • 56% (9 out of 16) of generated TIL products demonstrated tumor reactivity.
  • Tumor reactivity in TILs correlated with higher T cell infiltration and increased CD25 expression on CD8+ T cells in the tumor.
  • Despite the capacity for cytokine production, TIL products failed to produce significant amounts of IFN-γ, TNF-α, or IL-2 in response to autologous tumor digests.

Conclusions:

  • RCC TIL products contain tumor-reactive T cells, indicating their potential therapeutic value.
  • The restricted tumor-specific cytokine production by TILs suggests the presence of immunosuppressive factors within the RCC tumor microenvironment.
  • Further investigation into these immunosuppressive factors and optimization of TIL culture conditions are crucial for enhancing the efficacy of TIL therapy in RCC.
Keywords:
CD137RCCTIL therapydysfunctional T cellsimmune compositionimmunotherapy

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