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Method for determining TAT cells

A TAT-TCR, cell technology, applied in the field of determining TAT cells in blood, can solve the problems of cumbersome experiments, low throughput, and no way to cover T cells.

Pending Publication Date: 2022-06-07
TSINGHUA UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

Such a method has low throughput, cumbersome experiments and no way to cover all T cells related to tumor recognition

Method used

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  • Method for determining TAT cells

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0087] Example 1: Determination of TAT cells and TAT-TCR sequences

[0088] The inventors collected the TCR sequencing data of more than 100 cases of tumor tissue / peripheral blood pairings from the ImmuneACCESS public database, and divided all TCR clones into different subgroups based on the CDR3 sequence information. Subsequently, the inventors collected TCR sequencing data of more than 500 PBMC samples from normal healthy people from the ImmuneACCESS database. The TCR sequences present in the above-mentioned normal healthy human PBMC samples were excluded from the TCR sequences present in both PBMC (peripheral blood mononuclear cells) and TIL (tumor infiltrating T cells), and the resulting TCR sequences were defined as TAT-TCR sequences . T cells containing the TAT-TCR sequence were defined as TAT ​​cells ( figure 1 ).

Embodiment 2

[0089] Example 2: Assessment of Cancer Risk Using TAT-TCR Sequences

[0090] The inventors followed the data filtering and screening steps as shown in the figure below ( figure 1 ), a TAT-TCR-based binary prediction model was constructed to predict the probability that each TCR is a tumor-related TCR.

[0091] Subsequently, the inventor designed a TCR Repertoire Risk Score (TRRS) to quantitatively evaluate the enrichment degree of tumor-related T lymphocytes in the peripheral blood of patients. The specific calculation method is as follows: for each patient sample, the inventor uses the constructed The binary classification model predicts each TCR sequence detected in its PBMC, and obtains the probability that the TCR sequence is TAT; then under a given probability threshold (66% or 75%), we calculate that the patient is predicted as The number of TAT sequences a; next, we calculate the number b of TCR sequences (obtained from the above-mentioned public database) in the PBM...

Embodiment 3

[0093] Example 3: Analysis of clonal proliferation ability of TAT cells

[0094] The inventors analyzed the clonal proliferation of different T cell subsets by using the LymphoSeq R package (https: / / github.com / davidcoffey / LymphoSeq).

[0095] The inventors found that the clonal proliferation of T-cell subsets that share TCR sequences co-existing in the microenvironment of blood and tumor infiltration is higher, especially the clonal proliferation of such TAT cell subsets derived from PBMC is higher, indicating that the clonal proliferation is higher. This type of T cell subsets (TAT cells) have stronger binding ability to tumor-associated antigens and have stronger tumor-killing activity.

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Abstract

The invention provides a method for determining TAT cells. Compared with non-cancer related T cells, the TAT cell is expected to have higher specific binding capacity with cancer cells and higher capacity of killing the cancer cells. Meanwhile, the TAT-TCR sequence contained in the TAT cell can also be used or combined with transcriptome information for cancer screening, and the method is high in sensitivity and specificity. Only the peripheral blood sample of a subject needs to be collected, the invasive property is small, more information can be utilized, an existing tumor liquid biopsy method can be well supplemented, early-stage asymptomatic tumors are potentially detected, cancer diagnosis and treatment are integrated, and important application value is achieved.

Description

technical field [0001] The present invention provides a method for determining TAT cells in blood, and relates to the fields of cancer treatment, screening, detection and evaluation. Background technique [0002] Tumor liquid biopsy is a promising technique in the current cancer screening field. It can collect patient samples in a non-invasive manner, which is easy to operate and less invasive to patients. In the past, the technical means of tumor liquid biopsy based on serum cancer markers, cell-free DNA (cfDNA), circulating tumor cells (CTC), etc., were mostly based on tumor-related characteristics, and could not be effectively detected in the early stage of tumor development. , the signal-to-noise ratio is very low. The body's immune system has the function of recognizing tumor antigens and eliminating them, especially the adaptive immune response mediated by T lymphocytes, which can rapidly activate the immune response and prevent disease progression. Therefore, theore...

Claims

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Application Information

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IPC IPC(8): C12N5/0783C12Q1/6869C12Q1/6886G16B30/10G06N3/04
CPCC12N5/0636C12Q1/6869C12Q1/6886G16B30/10C12Q2600/158G06N3/045C12Q2535/122
Inventor 蓝勋季凡森陈琳罗斌
Owner TSINGHUA UNIV
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