Application of ARG1 in predicting curative effect of triple negative breast cancer immunotherapy

Abstract

The invention relates to an application of ARG1 in predicting the curative effect of triple negative breast cancer immunotherapy. Specifically provided is a use of a substance for specifically detecting ARG1 in a sample in the preparation of a kit, characterized in that the kit is used for predicting the therapeutic effect of immunotherapy on triple negative breast cancer (TNBC) patients. The technical scheme provided by the invention can better predict the curative effect of new adjuvant immunotherapy in triple negative breast cancer.

Description

Technical Field

[0001] The present invention relates to the field of disease treatment, and particularly to the application of ARG1 in predicting the efficacy of immunotherapy for triple-negative breast cancer. Background Art

[0002] Breast cancer is a global disease, with its incidence ranking first among female malignancies globally. Currently, breast cancer is clinically classified into Luminal type, HER2 overexpression type, and triple-negative breast cancer (TNBC). Clinical trial results show that adding anti-PD-1 / PD-L1 therapy to chemotherapy can significantly improve the progression-free survival of advanced TNBC patients and the pathological remission rate of tumors in the neoadjuvant treatment stage. That is, immunotherapy is changing the treatment pattern of TNBC. Efficacy prediction markers are an important part of immunotherapy. Using effective markers to screen out patients who are more likely to benefit is an important research direction to improve the efficacy of TNBC immunotherapy at present. However, the predictive efficacy of multiple current efficacy prediction markers is still controversial. Therefore, finding more effective efficacy prediction markers and more accurately and effectively screening out the possible beneficiary population of immunotherapy is an urgent problem to be solved. Summary of the Invention

[0003] Aiming at the defects of the prior art, the present invention detects the baseline plasma protein abundance of TNBC patients before neoadjuvant immunotherapy by PEA technology and finds that arginase 1 can be used as a marker for predicting the efficacy of neoadjuvant immunotherapy, that is, the ARG1 protein abundance before treatment can indicate and predict the efficacy of neoadjuvant immunotherapy.

[0004] The first aspect of the present invention provides the use of a substance for specifically detecting ARG1 in a sample in the preparation of a kit for predicting the efficacy of immunotherapy for triple-negative breast cancer (TNBC) patients.

[0005] In one or more embodiments, the immunotherapy is immunotherapy targeting PD-1 and / or PD-L1.

[0006] In one or more embodiments, the drug for the immunotherapy is a PD-1 antibody. Preferably, the PD-1 antibody is Toripalimab or Camrelizumab.

[0007] In one or more embodiments, the patient also receives chemotherapy before, during, or after receiving immunotherapy, and the drugs for chemotherapy are selected from any one or more of the following: epirubicin, cyclophosphamide, paclitaxel. In one or more embodiments, the drugs for chemotherapy include drugs selected from any one of the following groups: (1) epirubicin and cyclophosphamide, (2) paclitaxel, (3) epirubicin, cyclophosphamide, and paclitaxel. In one or more embodiments, the paclitaxel is albumin-bound paclitaxel.

[0008] In one or more embodiments, the sample is plasma.

[0009] In one or more embodiments, the specific detection is to detect ARG1 or the mRNA encoding it.

[0010] In one or more embodiments, the substance for specifically detecting ARG1 is a primer or probe that specifically recognizes the coding sequence of ARG1, or an antibody that specifically targets ARG1.

[0011] In one or more embodiments, the antibody is an antibody suitable for PEA detection.

[0012] In one or more embodiments, the detection is selected from: mRNA detection, immunohistochemistry (IHC), enzyme-linked immunosorbent assay (ELISA), Western blot, or PEA.

[0013] The present invention also provides a method for predicting the efficacy of immunotherapy for triple-negative breast cancer, including detecting the content of ARG1 in a sample from a subject before performing immunotherapy.

[0014] In one or more embodiments, the immunotherapy is immunotherapy targeting PD-1 and / or PD-L1.

[0015] In one or more embodiments, the drug for immunotherapy is a PD-1 antibody. Preferably, the PD-1 antibody is Toripalimab or Camrelizumab.

[0016] In one or more embodiments, the patient also receives chemotherapy before, during, or after receiving immunotherapy, and the drugs for chemotherapy are selected from any one or more of the following: epirubicin, cyclophosphamide, paclitaxel. In one or more embodiments, the drugs for chemotherapy include drugs selected from any one of the following groups: (1) epirubicin and cyclophosphamide, (2) paclitaxel, (3) epirubicin, cyclophosphamide, and paclitaxel. In one or more embodiments, the paclitaxel is albumin-bound paclitaxel.

[0017] In one or more embodiments, the sample is plasma.

[0018] In one or more embodiments, the detection is of ARG1 or the mRNA encoding it.

[0019] In one or more embodiments, the substance for detecting ARG1 is a primer or probe that specifically recognizes the ARG1 coding sequence, or an antibody that specifically targets ARG1.

[0020] In one or more embodiments, the antibody is an antibody suitable for PEA detection.

[0021] In one or more embodiments, the detection is selected from: mRNA detection, immunohistochemistry (IHC), enzyme-linked immunosorbent assay (ELISA), Western blot, or PEA.

[0022] The present invention also provides a method for selecting or assisting in selecting an immunotherapy regimen for triple-negative breast cancer, comprising:

[0023] (1) obtaining the content of ARG1 in a sample from the subject before immunotherapy; and

[0024] (2) if the content of ARG1 before immunotherapy is significantly increased compared to the reference, selecting or assisting in selecting the immunotherapy measure.

[0025] In one or more embodiments, the immunotherapy is immunotherapy targeting PD-1 and / or PD-L1.

[0026] In one or more embodiments, the drug for the immunotherapy is a PD-1 antibody. Preferably, the PD-1 antibody is Toripalimab or Camrelizumab.

[0027] In one or more embodiments, the patient also receives chemotherapy before, during, or after receiving immunotherapy, and the drugs for the chemotherapy are selected from any one or more of the following: epirubicin, cyclophosphamide, paclitaxel. In one or more embodiments, the drugs for the chemotherapy include drugs selected from any one of the following groups: (1) epirubicin and cyclophosphamide, (2) paclitaxel, (3) epirubicin, cyclophosphamide, and paclitaxel. In one or more embodiments, the paclitaxel is albumin-bound paclitaxel.

[0028] In one or more embodiments, the sample is plasma.

[0029] In one or more embodiments, the detection is of ARG1 or the mRNA encoding it.

[0030] In one or more embodiments, the substance for detecting ARG1 is a primer or probe that specifically recognizes the ARG1 coding sequence, or an antibody that specifically targets ARG1.

[0031] In one or more embodiments, the antibody is an antibody suitable for PEA detection.

[0032] In one or more embodiments, the detection is selected from: mRNA detection, immunohistochemistry (IHC), enzyme-linked immunosorbent assay (ELISA), Western blot, or PEA.

[0033] The present invention also provides a device for predicting the efficacy of immunotherapy for triple-negative breast cancer (TNBC) patients. The device includes a memory, a processor, and a computer program stored on the memory and executable on the processor. It is characterized in that when the processor executes the program, it implements a method for predicting the efficacy of immunotherapy for triple-negative breast cancer (TNBC) patients. The method includes the steps:

[0034] (1) Obtaining the content of ARG1 in a sample before immunotherapy of the subject; and

[0035] (2) If the content of ARG1 before immunotherapy is significantly increased compared to the reference, then the immunotherapy has a therapeutic effect on triple-negative breast cancer.

[0036] In one or more embodiments, the reference is ARG1 before immunotherapy of triple-negative breast cancer patients who are tolerant to the immunotherapy. The tolerance means that the patient does not achieve pathological complete remission after immunotherapy, that is, there are residual invasive tumor cells in the pathological examinations of the breast primary focus and axillary lymph node surgical specimens.

[0037] In one or more embodiments, the patient also receives chemotherapy before, during, or after receiving immunotherapy. The drugs for chemotherapy are selected from any one or more of the following: epirubicin, cyclophosphamide, paclitaxel. In one or more embodiments, the drugs for chemotherapy include drugs selected from any one of the following groups: (1) epirubicin and cyclophosphamide, (2) paclitaxel, (3) epirubicin, cyclophosphamide, and paclitaxel. In one or more embodiments, the paclitaxel is albumin-bound paclitaxel.

[0038] In one or more embodiments, the sample is plasma.

[0039] In one or more embodiments, the detection is to detect ARG1 or the mRNA encoding it.

[0040] In one or more embodiments, the substance for detecting ARG1 is a primer or probe that specifically recognizes the coding sequence of ARG1, or an antibody that specifically targets ARG1.

[0041] In one or more embodiments, the antibody is an antibody suitable for PEA detection.

[0042] In one or more embodiments, the detection is selected from: mRNA detection, immunohistochemistry (IHC), enzyme-linked immunosorbent assay (ELISA), Western blot, or proximity extension assay (PEA).

[0043] In one or more embodiments, having a therapeutic effect means achieving a pathological complete remission statistically, that is, there are no residual invasive tumor cells in the pathological examinations of the surgical specimens of the primary breast lesion and axillary lymph nodes.

[0044] The present invention also provides a kit, comprising a substance for specifically detecting ARG1 in a sample and an immunotherapeutic drug, and optionally further comprising a chemotherapeutic drug.

[0045] In one or more embodiments, the immunotherapeutic drug is a PD-1 antibody. Preferably, the PD-1 antibody is Toripalimab or Camrelizumab.

[0046] In one or more embodiments, the patient also receives chemotherapy before, during, or after receiving immunotherapy. The drugs for the chemotherapy are selected from any one or more of the following: epirubicin, cyclophosphamide, paclitaxel. In one or more embodiments, the drugs for the chemotherapy include drugs selected from any one of the following groups: (1) epirubicin and cyclophosphamide, (2) paclitaxel, (3) epirubicin, cyclophosphamide, and paclitaxel. In one or more embodiments, the paclitaxel is albumin-bound paclitaxel.

[0047] In one or more embodiments, the sample is plasma.

[0048] In one or more embodiments, the specific detection is to detect ARG1 or the mRNA encoding it.

[0049] In one or more embodiments, the substance for specifically detecting ARG1 is a primer or probe that specifically recognizes the coding sequence of ARG1, or an antibody that specifically targets ARG1.

[0050] In one or more embodiments, the antibody is an antibody suitable for PEA detection.

[0051] In one or more embodiments, the detection is selected from: mRNA detection, immunohistochemistry (IHC), enzyme-linked immunosorbent assay (ELISA), Western blot, or proximity extension assay (PEA).

[0052] Advantages of the present invention: By comparing the differences in ARG1 content before treatment, the present invention can better predict the efficacy of neoadjuvant immunotherapy for triple-negative breast cancer.

[0053] It should be understood that within the scope of the present invention, the above-mentioned technical features of the present invention and the technical features specifically described hereinafter (such as in the embodiments) can be combined with each other to form new or preferred technical solutions. BRIEF DESCRIPTION OF THE DRAWINGS

[0054] Figure 1 : The patients with neoadjuvant immunotherapy were divided into two groups according to the final efficacy: pathological complete remission and non-pathological complete remission. The differences in baseline plasma proteins before treatment between the two groups were compared by Wilcoxon rank sum test, and the plasma protein ARG1 with high efficacy prediction value was obtained.

[0055] Figure 2 : The predictive efficacy of ARG1 was evaluated using the ROC curve. The AUC value in the training set was 0.6653, indicating that ARG1 has good efficacy prediction ability.

[0056] Figure 3 : The predictive efficacy of ARG1 was evaluated using the ROC curve. The AUC value in the validation set was 0.641, indicating that ARG1 has good efficacy prediction ability. DETAILED DESCRIPTION OF THE INVENTION

[0057] The present invention explores the relationship between plasma protein abundance and the prediction of neoadjuvant immunotherapy. The aim is to non-invasively and repeatedly detect all the proteins expressed in the plasma and serum of the target population, find their differential proteins, identify the proteins related to diseases, and open up new ways for studying the pathophysiological mechanisms of diseases, early diagnosis specific markers, drug action targets, efficacy prediction markers, etc. The inventor found that the content of ARG1 can well predict the efficacy of neoadjuvant immunotherapy for triple-negative breast cancer.

[0058] As used herein, "triple-negative breast cancer (TNBC)" refers to breast cancer in which the immunohistochemical examination results of cancer tissues are negative for estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (Her-2). The inventor found that the plasma protein ARG1 abundance in triple-negative breast cancer patients before neoadjuvant immunotherapy was significantly higher than that of the reference, indicating a high value for predicting efficacy.

[0059] Therefore, the present invention provides a method for predicting the efficacy of immunotherapy for patients with triple-negative breast cancer (TNBC), including: (1) obtaining the content of ARG1 in the sample of the subject before immunotherapy; and (2) if the content of ARG1 before immunotherapy is significantly higher than that of the reference, selecting or assisting in selecting the immunotherapy measure.

[0060] The level of ARG1 can be determined by detecting the content of ARG1 protein or its encoded mRNA. For example, the level of ARG1 can be detected by the following methods: mRNA detection, immunohistochemistry (IHC), enzyme-linked immunosorbent assay (ELISA), Western blot, proximity extension assay (PEA). These methods are well-known to those skilled in the art. An exemplary immunohistochemistry kit is Arginase1 Polyclonal Antibody, and an exemplary ELISA kit is: Human Arginase-1 (ARG1) ELISA kit. In this article, "substances that specifically detect ARG1 in a sample" include reagents used in these methods that can target, recognize, bind, or distinguish ARG1, such as anti-ARG1 antibodies, primers, or probes for detecting mRNA content. Those skilled in the art know how to obtain anti-ARG1 antibodies, primers, or probes suitable for these methods and their sequences.

[0061] The proximity extension assay (PEA) technology is used for experimental detection through a QPCR platform. The PEA technology has characteristics such as high throughput, high specificity, and high sensitivity. Its principle is as follows: In the experimental design, a pair of antibodies that specifically recognize the target protein is used, and a nucleotide sequence is linked to the end of the antibody. Only when the dual antibodies labeled with unique nucleic acid sequence information correctly recognize the target protein can the nucleotides carried by the antibody pair undergo base complementary pairing to form a double strand, thereby performing subsequent PCR amplification and QPCR detection, and realizing the conversion of the quantitative detection of the target protein into the real-time quantitative detection of oligonucleotides.

[0062] The steps of PEA include: (1) incubation, (2) extension, and (3) detection. In one or more embodiments, step (1) includes specific antibody pairs recognizing and binding to the corresponding target protein, and at the same time, the base sequences at the ends undergo complementary pairing; step (2) includes the amplification and enrichment of DNA fragments; step (3) includes performing QPCR detection using the enriched DNA fragments as templates and collecting detection data (QPCR data).

[0063] In this article, a significant increase means that: compared with the control sample, the increase amplitude of the abundance of ARG1 is ≥10%, preferably ≥20%, preferably ≥50%, more preferably ≥80%, and most preferably ≥100%.

[0064] As used herein, "immunotherapy" includes immunotherapy targeting any triple-negative breast cancer-related target. An exemplary target is an immune checkpoint (such as PD-1 or PD-L1). It is known in the art that PD-1 and PD-L1 are ligand-receptor pairs. Therefore, when one of them can be used as a target for immunotherapy, the other can generally also be used as an immunotherapy target. Immunotherapy drugs include immune checkpoint inhibitors, tumor vaccines, cellular immunotherapy, and non-specific immunomodulators. Immune checkpoint inhibitors can be antibodies. When immunotherapy is cellular immunotherapy, the immunotherapy drugs include immune effector cells, such as T cells, NK cells, and TIL cells. Immune effector cells as drugs can be modified, such as CAR-T, CAR-NK, etc.

[0065] In one or more embodiments, the patient also receives chemotherapy before, during, or after receiving immunotherapy. The chemotherapy regimen can be adjusted by a physician based on various factors (such as patient gender, age, medical history, allergy history, medication history, disease severity, etc.). Exemplary chemotherapy drugs include epirubicin, cyclophosphamide, and paclitaxel. In one or more embodiments, the chemotherapy drugs include drugs selected from any one of the following groups: (1) epirubicin and cyclophosphamide, (2) paclitaxel, (3) epirubicin, cyclophosphamide, and paclitaxel. In one or more embodiments, the paclitaxel is albumin-bound paclitaxel.

[0066] In one or more embodiments, the treatment regimen for the patient is: epirubicin and cyclophosphamide; sequential albumin-bound paclitaxel and Toripalimab. For example, the treatment regimen for the patient is: epirubicin and cyclophosphamide every 14 days as a cycle for a total of 4 cycles; sequential albumin-bound paclitaxel once a week for 3 consecutive weeks as a cycle for a total of 4 cycles, and Toripalimab every 3 weeks as a cycle for a total of 4 cycles.

[0067] In one or more embodiments, the treatment regimen for the patient is Camrelizumab and a chemotherapy regimen. For example, the treatment regimen for the patient is Camrelizumab every 3 weeks as a cycle for a total of 8 cycles, combined with the patient's respective chemotherapy regimen.

[0068] The term "sequential therapy" refers to when using drugs to treat a disease, initially parenteral administration (intravenous injection) is used (for example, for 2 - 3 days), and after the clinical symptoms are basically stable and the condition improves, oral drug treatment is switched to.

[0069] In this article, the samples are from mammals, preferably humans. The samples can be from any organ (such as bone marrow), tissue (such as epithelial tissue, connective tissue, muscle tissue, and nerve tissue), cells (such as red blood cells), or body fluids (such as blood (including peripheral blood), plasma, serum, tissue fluid, urine), as long as the samples contain plasma proteins. Plasma proteins refer to the protein part in plasma. Plasma proteins are a general term for various proteins and can be divided into several components such as albumin, globulin, and fibrinogen.

[0070] The term "subject" or "patient" may refer to a patient or other animal, especially a mammal, such as a human, dog, monkey, cow, horse, etc., who undergoes the plasma protein detection of the present invention for the treatment, prediction, and / or prevention of the diseases or conditions of the present invention.

[0071] In this article, "reference" is a reference value for comparing the ARG1 content. If it is higher than or equal to this reference value, the result of the patient receiving immunotherapy is expected to be pathological complete remission; otherwise, it is expected to be non-pathological complete remission. The reference can be the plasma ARG1 content of triple-negative breast cancer patients who are tolerant to immunotherapy before immunotherapy, or the average value or statistical threshold of plasma ARG1 of multiple triple-negative breast cancer patients who are tolerant to immunotherapy, or the average value of plasma ARG1 of triple-negative breast cancer patients who are tolerant to immunotherapy in the population. The term "tolerant" means that the patient does not achieve pathological complete remission after immunotherapy, that is, there are residual invasive tumor cells in the pathological examinations of the breast primary focus and axillary lymph node surgical specimens.

[0072] The reference can also be the prediction threshold of ARG1 evaluated by the ROC curve. The method of calculating the threshold based on the existing data is common knowledge in the art.

[0073] The present invention also provides a method for screening the plasma proteins with high abundance, which includes the steps of: (1) detecting the baseline plasma protein abundance of disease patients before neoadjuvant immunotherapy by the PEA technique; (2) dividing some patients into two groups of pathological complete remission and non-pathological complete remission according to the final efficacy; (3) comparing the baseline plasma protein differences before treatment between the two groups by the Wilcoxon rank sum test; (4) analyzing the efficacy prediction ability of plasma proteins by the Receiver Operating Characteristic Curve (ROC) curve; and (5) evaluating the AUC value of the ROC curve.

[0074] The present invention also provides a kit, which contains substances for specifically detecting ARG1 in a sample as described herein and an immunotherapeutic drug, and optionally also contains a chemotherapeutic drug. The kit is used for predicting the efficacy of immunotherapy for triple-negative breast cancer (TNBC) patients. The kit can be used in a method for selecting or assisting in selecting an immunotherapy regimen for triple-negative breast cancer, and the method includes: (1) obtaining the content of ARG1 in a sample from a subject before immunotherapy; and (2) if the content of ARG1 before immunotherapy is significantly increased compared to a reference, selecting or assisting in selecting the immunotherapy measure. The kit may also contain: reagents for obtaining a sample, reagents for purifying proteins, reagents for enriching ARG1 protein, reagents for extracting RNA, etc.

[0075] The present invention will be further described below in conjunction with specific embodiments. It should be understood that these embodiments are only used to illustrate the present invention and not to limit the scope of the present invention. The experimental methods without specific conditions noted in the following embodiments are generally carried out under conventional conditions such as those described in Molecular Cloning: A Laboratory Manual, Third Edition, edited by J. Sambrook et al., Science Press, 2002, or according to the conditions recommended by the manufacturer.

[0076] Examples

[0077] Example 1

[0078] 1. Research subjects: 73 TNBC patients who received neoadjuvant immunotherapy and corresponding plasma samples before treatment. Among them, 50 patients had a treatment regimen of epirubicin (90 mg / m 2 ) plus cyclophosphamide (600 mg / m 2 ) every 14 days as a cycle, for a total of 4 cycles; sequential albumin-bound paclitaxel (125 mg / m 2 ) once a week for 3 consecutive weeks as a cycle, for a total of 4 cycles, and PD-1 monoclonal antibody (Toripalimab) (240 mg) every 3 weeks as a cycle, for a total of 4 cycles. 23 patients had a treatment regimen of Camrelizumab (200 mg) every 3 weeks as a cycle, for a total of 8 cycles, combined with an individualized chemotherapy regimen selected by the doctor. The samples were from clinical trials, as shown in Table 1.

[0079] Table 1

[0080]

[0081] 2. Experimental method: The PEA method (Olink, Cat. No: 95311) was used to detect the plasma protein content of patients. The experimental detection mainly consisted of three major steps: incubation, extension, and detection. In the incubation stage, specific antibody pairs would recognize the corresponding target protein (ARG1) and bind to it, while the terminal base sequences would perform complementary pairing; the extension stage was mainly for the amplification and enrichment of DNA fragments; in the detection stage, QPCR detection was performed using the enriched DNA fragments as templates, and the detection data (QPCR data) were collected.

[0082] 3. Analysis method: The patients with neoadjuvant immunotherapy were divided into two groups according to the final efficacy: pathological complete remission and non-pathological complete remission. Among them, pathological complete remission (pCR): there were no residual invasive tumor cells in the pathological examinations of the breast primary tumor and axillary lymph node surgical specimens. The baseline plasma protein differences before treatment between the two groups were compared by Wilcoxon rank sum test to obtain plasma proteins with high efficacy prediction value; in addition, all samples were divided into a training set (49 cases) and a validation set (24 cases) according to a ratio of 2:1, and the prediction efficacy of plasma proteins was evaluated using the ROC curve, and the AUC value of the ROC curve was evaluated.

[0083] 4. Detection results: It was found that there were significant differences in the content of plasma protein arginase 1 (Arginase 1, ARG1) before treatment between the pathological complete remission and non-pathological complete remission groups. Compared with patients with non-pathological complete remission, patients with pathological complete remission had a higher pre-treatment ARG1 abundance (p = 0.02), that is, the pre-treatment ARG1 protein abundance could suggest and predict the efficacy of neoadjuvant immunotherapy. As Figure 2 and Figure 3 shown, the area under the curve (Area Under Curve, AUC) value of ARG1 was 0.6653 in the training set and 0.641 in the validation set, with good efficacy prediction ability. The prediction threshold was 2.3.

Claims

1. Use of a substance for specifically detecting ARG1 in a sample in the preparation of a kit, characterized in that, the kit is used for predicting the efficacy of immunotherapy for triple-negative breast cancer (TNBC) patients.

2. The use according to claim 1, characterized in that, the immunotherapy is immunotherapy targeting PD-1 and / or PD-L1, preferably, the drug for the immunotherapy is a PD-1 antibody.

3. The use according to claim 1, characterized in that, the detection is selected from: mRNA detection, immunohistochemistry (IHC), enzyme-linked immunosorbent assay (ELISA), Western blot or proximity extension assay (PEA), preferably, the substance for specifically detecting ARG1 is a primer or probe specifically recognizing the coding sequence of ARG1, or an antibody specifically targeting ARG1.

4. The use according to claim 1, characterized in that, the sample is plasma.

5. A device for predicting the efficacy of immunotherapy for triple-negative breast cancer (TNBC) patients, the device comprising a memory, a processor, and a computer program stored on the memory and executable on the processor, characterized in that, the method for predicting the efficacy of immunotherapy for triple-negative breast cancer (TNBC) patients implemented when the processor executes the program, the method comprising the steps of: (1) obtaining the content of ARG1 in the sample before immunotherapy of the subject; and (2) if the content of ARG1 before immunotherapy is significantly increased compared to the reference, then the immunotherapy has a therapeutic effect on triple-negative breast cancer.

6. The device according to claim 5, characterized in that, the detection is selected from: mRNA detection, immunohistochemistry (IHC), enzyme-linked immunosorbent assay (ELISA), Western blot or proximity extension assay (PEA), preferably, the substance for detecting ARG1 is a primer or probe specifically recognizing the coding sequence of ARG1, or an antibody specifically targeting ARG1.

7. The device according to claim 5, characterized in that, the sample is plasma.

8. A kit, comprising a substance for specifically detecting ARG1 in a sample and an immunotherapy drug, optionally further comprising a chemotherapy drug.

9. The kit according to claim 8, characterized in that, the immunotherapy drug is a PD-1 antibody.

10. The kit according to claim 8, characterized in that, the detection is selected from: mRNA detection, immunohistochemistry (IHC), enzyme-linked immunosorbent assay (ELISA), Western blot or proximity extension assay (PEA), preferably, the substance for specifically detecting ARG1 is a primer or probe specifically recognizing the coding sequence of ARG1, or an antibody specifically targeting ARG1.

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