Biomarker for predicting tumor immunotherapy response

A malignant tumor and immune checkpoint technology, applied in the field of biomarkers to predict the response of tumor immunotherapy, can solve the problem that lung cancer patients cannot benefit from it, and achieve the effect of enhancing the effect

Inactive Publication Date: 2021-12-10
SHANGHAI CHEST HOSPITAL
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Problems solved by technology

[0004] However, there are still many deficiencies in the above biomarkers
Although PD-L1, MSI, and TMB can predict the occurrence of immunotherapy response to a certain extent, they only show a good predictive effect in a small number of lung cancer patients, with high heterogeneity, that is, there are certain false positives and false negative rate, more lung cancer patients will not benefit from it

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  • Biomarker for predicting tumor immunotherapy response
  • Biomarker for predicting tumor immunotherapy response
  • Biomarker for predicting tumor immunotherapy response

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Embodiment 1

[0029] 1 Materials and methods

[0030] 1.1 Preparation of single cell suspension of surgically resected lung cancer samples

[0031] 1) Sample preparation

[0032] Two pairs (primary lung tumor [pT1N0M0] and matched normal lung tissue) lung samples were collected and immediately transferred for single cell isolation. Tumor tissue and normal lung tissue adjacent to the tumor were obtained during surgery at Huadong Hospital (Shanghai, China). Tumor samples were collected from three different sites in the tumor bed. The normal lung tissue was at least 5 cm away from the malignant tumor area. Tissues were rinsed with cold PBS (Cytiva, SH30256.01) to wash away blood and dead cells. Then, they were placed in 1.5 mL of chilled tissue storage solution (Miltenyi, 130-100-008) and transferred to the laboratory on ice. Mince tissue into small pieces (less than 1 mm) within 5 minutes 3), adding digestion buffer (4.7 mL DMEM (Cytiva, SH30243.01) + 325 μL enzyme mix (Miltenyi, 130-09...

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Abstract

The invention relates to a biomarker for predicting tumor immunotherapy response. Researches find that the expression level of THBS2 in lung cancer tumors is related to the clinical immunotherapy reaction effect; THBS2 can inhibit T cell proliferation of a non-small cell lung cancer patient. THBS2 is related to the expression of immune escape molecules; THBS2 is related to CD8+T and CD19+B cell infiltration reduction in lung adenocarcinoma tumors; THBS2 is derived from a partial subset of cancer-associated fibroblasts (CAF) in a tumor microenvironment, and the partial subset is different from a subset defined by a classical CAF marker. Based on the research results, the invention provides application of a reagent for detecting the expression quantity of the marker THBS2 in preparation of a product for evaluating the response of malignant tumors to immunotherapy and application of THBS2 positive expression CAF as a potential target in overcoming immunotherapy drug resistance.

Description

technical field [0001] The present invention relates to the field of biomedicine, in particular to a biomarker for predicting tumor immunotherapy response. Background technique [0002] Immune checkpoint inhibitor (ICI) is a new breakthrough in the field of tumor treatment. However, not all patients can benefit, so it is necessary to predict the efficacy of immunotherapy in patients before treatment, so as to achieve the purpose of precise treatment. [0003] Currently clinically approved biomarkers for predicting response to immunotherapy include PD-L1 expression levels in patient tumor tissue, microsatellite instability (MSI) or tumor mutational burden (TMB). The results of clinical trials in NSCLC patients show that: if the expression rate of PD-L1 in tumor tissue exceeds 50%, PD-1 inhibitors can be used as the first choice of treatment, and if the expression rate of PD-L1 is greater than 1%, immune checkpoint inhibitors It can benefit lung cancer patients who fail firs...

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): G01N33/574C12Q1/6886A61K45/06A61P35/00
CPCG01N33/57415G01N33/57449G01N33/57438G01N33/57407G01N33/57484C12Q1/6886A61K45/06A61P35/00C12Q2600/158C12Q2600/106
Inventor 杨海堂姚烽孙贝贝
Owner SHANGHAI CHEST HOSPITAL
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