Tertiary Lymphoid Structures as a Predictive Biomarker

The tertiary lymphoid structure (TLS) has emerged as a prominent biomarker for assessing the response of various tumor structures to immune checkpoint therapy. Here at Creative Biolabs, we present crucial information about the role of TLS in tumor immunology and its significance as an immune intervention predictor biomarker.

TLS in Tumor Immunity

TLS represents an anatomical entity akin to secondary lymphoid structures, comprising tumor-infiltrating lymphocytes, including T-cells, B-cells, high endothelial venules, and DC cells. TLS serves to modulate the immune microenvironment by augmenting local immune responses and recruiting circulating immune cells, thus facilitating tumor clearance by means of infection control or rejection reactions.

The potential mechanisms through which TLS acts against cancer include:

Maintaining B cell maturation and antibody production within the tumor, resulting in a full B cell response, leading to direct anti-tumor effects.
Altering T cell activation and function in conjunction with other key immune components of TLS to improve ICB effects.

TLS and its components. (Zou, et al., 2022) Fig 1. TLS and its components.¹

TLS as a Predictive Biomarker

Substantial fundamental research has unequivocally demonstrated the association between TLS existence and favorable outcomes in PD-1-based or PD-1/CTLA-4 combination blockade therapies, validating the predictive role of TLS on the biology behaviors, treatment methods, and prognosis of various tumors:

Breast Cancer: TLS affects the ability of lymphocytes to enter solid tumors and initiate/maintain the host's anti-tumor environment.
Colon Cancer: TLS is highly correlated with newly established local disease and new metastases.
Renal Cancer: Patients with TLS positivity show a higher response rate and longer progression-free survival under ICB treatment.
Other tumor types: Mature TLS patients benefit most from checkpoint blockade in melanoma, soft tissue sarcoma, and non-small cell lung cancer, and improved objective tumor responses have been observed.

However, it is essential to note that TLS is a multi-cell dynamic structure with significant heterogeneity, and different molecular markers or datasets need to be considered for evaluation in different cancer types.

Antitumor effect of TLS. (Zhang, et al., 2023) Fig 2. Antitumor effect of TLS.²

Therapeutic Induction of TLSs

Due to the extensive participation of TLS in anti-tumor responses, inducing TLS formation is considered a promising tumor intervention strategy:

Expression of relevant cytokines and chemokines can induce local TLS in mice models.
Anti-angiogenesis shared with PD-L1 blockade can induce TLS and enhance cytotoxic T cell activity.
Some standardized chemotherapy regimens lead to immune reconstruction and accompanying B cell infiltration, resulting in TLS formation.

Although inducing or enhancing TLS is beneficial for tumor control, the application of these strategies may also promote self-reactive immune responses, requiring additional scrutiny and research.

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At Creative Biolabs, we transcend mere theoretical support and offer a comprehensive range of advanced services in the realm of immune checkpoint. From biomarker identification and validation to preclinical investigations and clinical trial assistance, our multidimensional approach ensures unparalleled support throughout the entire process. Contact us now to explore the full potential of immune checkpoint immunotherapy.

References

Zou, Ji'an, et al. "Tertiary Lymphoid Structures: A Potential Biomarker for Anti-Cancer Therapy." Cancers 14.23 (2022): 5968.
Zhang, et al. "Tertiary lymphoid structures are critical for cancer prognosis and therapeutic response." Frontiers in Immunology 13 (2023): 1063711.

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