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Published on: January 26, 2024
Induction of tertiary lymphoid structures in tumor microenvironment to improve anti-tumoral immune checkpoint
Roman Vion1, Matthieu Roulleaux-Dugage2, Ronan Flippot3
1Department of Medical Oncology, Henri Becquerel Institute, Rouen University, Rouen, France; INSERM U1245, IRON, Université de Rouen, Rouen, France.
Abstract:
Immune checkpoint blockade (ICB) have revolutionized medical oncology, with the occurrence of cures in situations regarded as palliative. However, most patients develop resistance and the selection of responders remains difficult. The search for predictive biomarkers for immunotherapy has revealed that tertiary lymphoid structures (TLS) in the tumor microenvironment (TME) may be indicative of treatment effectiveness, since they may reflect the presence of an immune infiltrate with an anti-tumor effect. A better understanding of TLS neogenesis would help to establish anti-tumor strategies. For this purpose, this review outlines therapeutic modalities that could increase the immunogenicity and antigenicity of tumor cells, in particular immunogenic cell death (ICD), to turn "cold" tumors in "hot" tumors through interventions that promote the development of TLS. Second, the review describes the therapeutic strategies to enhance immune response against tumors, especially the resources to induce TLS, to strengthen cytotoxic T response / decrease Tregs and to promote the homing of immune cells. Future strategies should focus on a synergistic tactic combining both the enhancement of cancer cell immunogenicity and the stimulation of the immune system. PROVENANCE AND PEER REVIEW: Review commissioned by Aurelien Marabelle; externally peer reviewed.
Insights
Immune checkpoint blockade (ICB) shows promise in cancer treatment but faces resistance. Tertiary lymphoid structures (TLS) in tumors may predict response by indicating an anti-tumor immune infiltrate, guiding new therapeutic strategies.
Area of Science:
- Oncology
- Immunology
- Cancer Research
Background:
- Immune checkpoint blockade (ICB) has transformed cancer therapy, offering cures for some patients.
- However, resistance to ICB is common, and identifying responders remains challenging.
- Tertiary lymphoid structures (TLS) within the tumor microenvironment (TME) are emerging as potential predictive biomarkers for immunotherapy effectiveness.
Purpose of the Study:
- To review therapeutic strategies aimed at enhancing anti-tumor immunity.
- To explore methods for increasing tumor cell immunogenicity and antigenicity.
- To discuss interventions promoting TLS neogenesis for improved immunotherapy outcomes.
Main Methods:
- Review of existing literature on immunotherapy, tumor microenvironment, and TLS.
- Analysis of therapeutic modalities that induce immunogenic cell death (ICD).
- Examination of strategies to enhance immune responses, including TLS induction and immune cell modulation.
Main Results:
- TLS presence correlates with immune infiltrate and potential treatment effectiveness.
- Therapeutic interventions can convert "cold" tumors to "hot" tumors by promoting TLS.
- Strategies exist to enhance cytotoxic T cell responses and reduce regulatory T cells (Tregs).
Conclusions:
- Understanding TLS neogenesis is crucial for developing effective anti-tumor strategies.
- Combining approaches to enhance cancer cell immunogenicity and stimulate the immune system offers a promising synergistic tactic.
- Future research should focus on integrated strategies to overcome immunotherapy resistance.
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