A device for predicting the therapeutic effect of immune checkpoint blockade therapy and its application

A technology for immune checkpoints and treatment effects, which is applied in the directions of measuring devices, microbial measurement/inspection, disease diagnosis, etc., can solve problems such as unsatisfactory prediction effects, and achieve the effects of simple operation, good correlation and strong applicability

Active Publication Date: 2022-03-29
PEKING UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Due to indirectness, the protein abundances of TMB and PD-L1 are predictors that are not ideal for the treatment of many cancer patients

Method used

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  • A device for predicting the therapeutic effect of immune checkpoint blockade therapy and its application
  • A device for predicting the therapeutic effect of immune checkpoint blockade therapy and its application
  • A device for predicting the therapeutic effect of immune checkpoint blockade therapy and its application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0073] This example verifies the correlation between the expression of a single gene of CXCL13 and the response rate of immunotherapy.

[0074] The gene expression data from 18 cancer types in the TCGA database were analyzed, and the results were as follows: figure 1 shown. It can be seen from the figure that the gene expression of CXCL13 in cancer samples (horizontal axis) is poorly correlated with the response rate of the cancer type to immunotherapy (vertical axis). The P value was 0.14, indicating that the gene expression of CXCL13 was not significantly correlated with the response rate of immunotherapy at the pan-cancer level, indicating that the expression of a single gene of CXCL13 is a poor predictor.

Embodiment 2

[0076] This example verifies the correlation between the proportion of CD3 and CXCL13 double positive cells in CD3 T cells or the proportion of CD8 and CXCL13 double positive cells in CD8 T cells and the response rate of immunotherapy.

[0077] From 13 cancer types (including breast cancer, esophageal cancer, liver cancer, lung squamous cell carcinoma, lung adenocarcinoma, melanoma, MSI colorectal cancer, MSS colorectal cancer, nasopharyngeal cancer, ovarian cancer, pancreatic cancer, kidney cancer and Endometrial cancer), each cancer type contains tumor samples from multiple patients. Calculate the median of CD3 and CXCL13 double positive cells in CD3 T cells or CD8 and CXCL13 double positive cells in CD8 T cells for each cancer type in multiple tumor samples, and compare the cancer type The response rate of the reported immune checkpoint blockade therapy was compared, and the results were as follows: figure 2 shown.

[0078] It can be seen from the figure that the proport...

Embodiment 3

[0080] In this example, the proportion of CD3 and CXCL13 double positive cells in CD3 T cells or the proportion of CD8 and CXCL13 double positive cells in CD8 T cells is used as the basis to predict the response of samples to immunotherapy, and the accuracy of the prediction Sex is tested.

[0081] Collect single-cell transcriptome datasets from 9 immune checkpoint blockade therapies in 5 cancers, including non-small cell lung cancer (NSCLC), breast cancer (Breast cancer), basal cell carcinoma (BCC), squamous cell carcinoma ( SCC) and renal cell carcinoma (Renal cell carcinoma), these data contain 229 samples from 103 patients before and after treatment. Combining data from multiple cancer types revealed the proportion of CD3 and CXCL13 double positive cells among CD3 T cells and the proportion of CD8 and CXCL13 double positive cells among CD8 T cells in pretreatment tumor samples from patients who responded to treatment. significantly higher than non-responding patients (e.g...

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Abstract

The present invention provides a device for predicting the therapeutic effect of immune checkpoint blockade therapy and its application. The device for predicting the therapeutic effect of immune checkpoint blockade therapy includes: a detection module: detecting CD3 and CXCL13 double positive cells and / or CD8 and CXCL13 double-positive cells, and count the proportion of CD3 and CXCL13 double-positive cells in CD3 T cells and / or the proportion of CD8 and CXCL13 double-positive cells in CD8 T cells; analysis module: according to the statistical results , to judge. The present invention selects the ratio of CD3 and CXCL13 double-positive cells in CD3 T cells and / or the ratio of CD8 and CXCL13 double-positive cells in CD8 T cells as a measure to predict the response of samples to immune checkpoint blockade therapy , the result is accurate and the applicability is strong.

Description

technical field [0001] The invention belongs to the technical field of immunotherapy, and in particular relates to a device for predicting the therapeutic effect of immune checkpoint blockade therapy and its application. Background technique [0002] Immune checkpoint blockade therapy has significantly improved the treatment effect of cancer, but this therapy is only effective for a part of tumor patients, so it is necessary to predict the response of cancer patients to this treatment. A commonly used assay is tumor mutational burden (TMB) (Yarchoan et al., 2017, NEJM). The higher the TMB, the more tumor antigens a tumor may have, and therefore the more tumor-specific T cells may be activated. Therefore, TMB can be detected by sequencing methods, and tumor patients with high TMB are more likely to be curative after receiving immunotherapy. [0003] In addition, there are similar detection indicators, such as the expression of PD-L1 in tumors (Martin et al., 2016, NEJM). C...

Claims

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Application Information

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IPC IPC(8): C12Q1/02
CPCG01N33/5005G01N2800/52
Inventor 刘宝琳张园园张泽民
Owner PEKING UNIV
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