TILs and Exclusion of TILs as Biomarkers of Response and Resistance

Tumor-Infiltrating Lymphocytes (TIL) are considered as one of the effective predictive molecules for immune checkpoint blockade response. Here at Creative Biolabs, we aim to introduce relevant information about TIL and exclude TIL as a marker for response and resistance, in order to help you better understand the prediction of ICB response and reasonably choose tumor intervention strategies.

CD8+ T cells states associated with clinical outcome. (Feldman, et al., 2018)Fig 1. CD8+ T cells states associated with clinical outcome.1

TIL as a predictive biomarker for ICB response

The presence of TIL has been shown to be associated with PD-L1 expression. Moreover, studies on the correlation of anti-CTLA-4 intervention strategy have found that the degree of ICT-induced tumor necrosis is directly correlated with the ratio of intra-tumor CD8+ cells/FOXP3+ Tregs. These facts demonstrate the potential of TIL as a biomarker for predicting the efficacy of tumor intervention.

TIL and PD-L1 co-prediction

Both TIL and PD-L1 as independent biomarkers for predicting tumor intervention have certain limitations, while combining the two as co-predictive indicators shows accurate predictive ability. Cancer microenvironment classification methods based on PD-L1 and TIL expression have been proposed.

T1 (PD-L1 and TIL negative)

  • Most likely to have inherent resistance

T2 (PD-L1 and TIL positive)

  • Most likely to respond to ICB

T3 (PD-L1 negative and TIL positive)

  • Activation of interferon pathways to induce PD-L1 expression interventions, may increase ICB response

T4 (PD-L1 positive and TIL negative)

  • Induced local cell death and lymphocyte infiltration strategies may synergize with ICB

The co-predictive biomarkers of TIL and PD-L1 provide a new perspective for estimating the effect of ICB, and more predictive markers have been added to the standardized evaluation process.

TIL quantification and detection

The method of quantifying total TIL or immune cell-specific subgroups still needs standardization and prospective validation. Currently, standardized methods under development include:

  • Single-cell RNA sequencing of tumor-associated immune cells
  • Multiplex immunofluorescence
  • Measurement of tumor-infiltrating lymphocytes based on automated image analysis
  • Flow cytometry-based tumor immune cell profiling analysis

Our Services

At Creative Biolabs, we exceed the boundaries of theoretical support by offering comprehensive, high-level services in the field of immune checkpoint. Our team of proficient scientists and researchers offers expertise in experimental design, data analysis, and interpretation. From biomarker identification to personalized treatment strategies, our services encompass every aspect of immunotherapy research, driving innovation and achieving optimal therapeutic outcomes. Contact us today to explore the full potential of immune checkpoint methodologies.

Reference

  1. Feldman, Lu, et al. "Defining T cell states associated with response to checkpoint immunotherapy in melanoma." Cell. 175.4 (2018): 998-1013.

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