Global research trends on B7-H3 for cancer immunotherapy: A bibliometric analysis (2012-2022)

ABSTRACT

Immunotherapy has revolutionized cancer treatment. B7-H3 is a promising target for cancer immunotherapy (CI). The present study aimed to utilize bibliometric methods to assess the current research status and explore future trends in the use of B7-H3 for CI. We collected publications related to B7-H3/CI from the Clarivate Web of Science Core Collection database. VOSviewer, Microsoft Excel, the bibliometrix R package, and an online platform were used to conduct qualitative and visualized analyses of the literature. A total of 555 papers were analyzed, revealing a significant increase in annual publications since 2018. The most productive countries were China and the USA, and the leading institutions were Soochow University and Sichuan University. Zang and Ferrone were the most popular authors. Among the journals, Frontiers in Immunology had the highest number of papers, whereas Clinical Cancer Research was the most influential. Historical citation analysis reveals the development of B7-H3/CI. Top-cited papers and keyword analyses were performed to highlight current hotspots in the domain. Using cluster analysis, we classified all keywords into four clusters: “immunotherapy,” “co-stimulatory molecule,” “B7 family,” and “PD-L1.” Finally, Trends analysis suggested that future research might focus on “chimeric antigen receptor,” “pathways,” and “targeting B7-H3.” This is the first bibliometric crosstalk analysis between B7-H3 and CI. Our study illustrates that the topic of B7-H3/CI is very popular and has great clinical implications and that the number of correlative publications will continue to increase. B7-H3-based CI may lead to new research trends.

KEYWORDS:

• B7-H3
• cancer immunotherapy
• bibliometric
• trends
• CAR-T

Introduction

In the past decade, immune checkpoint inhibitors (ICIs), primarily targeting Programmed Death 1 (PD1), Programmed Death-Ligand 1 (PD-L1), and Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), have made significant strides in the treatment of various solid tumors, remodeling therapeutic practice in oncology.^1–4 Although ICIs show robust antitumor effects, their efficacy is limited by the heterogeneity of tumors, drug resistance, and adverse events.^5–7 Therefore, identifying other potential targets for cancer immunotherapy (CI) is critical.

CI depends on immune escape mechanisms, and the specific correction of immune deficiency to restore natural antitumor immunity and immune normalization is essential for the efficacy of CI.⁸ The B7 family is involved in the immune response by regulating the activation, proliferation, differentiation, and function of immune cells.⁹ Similar to the well-studied B7-H1(PD-L1), the B7 homolog 3 protein (B7-H3) is a member of the B7 family. B7-H3 is an immune checkpoint molecule functions as a co-stimulatory/co-inhibitory molecule and plays a contradictory role in the human immune system.¹⁰ It has received much attention in the past decade since the first identification in 2001.¹¹ The B7-H3 gene is located on chromosome 15,¹² and the B7-H3 protein is produced in both transmembrane or soluble isoforms.¹³ Transmembrane B7-H3 has 316 amino acids with a molecular weight of 45–66 kDa,¹⁴ which consists of an extracellular domain, a transmembrane domain, and a short intracellular domain.¹⁵ Soluble B7 - H3 (sB7-H3) has been detected in human serum and is produced by cleavage from the surface by matrix metalloproteinases (MMPs)¹⁶ or alternative splicing of introns.¹⁷

Accumulating evidence has demonstrated that B7-H3 weakens T-cell activation and increases regulatory T-cell infiltration, decreasing the efficacy of immunotherapy.^18,19 Moreover, B7-H3-mediated tumor glycolysis increases resistance to CI.^20,21 Several preclinical and clinical studies have demonstrated the feasibility of anti-B7-H3 therapy.²² Moreover, high levels of B7-H3 augment angiogenesis and reconstruct the extracellular matrix to promote metastasis, contributing to poor prognosis of patients.^23–25 Thus, B7-H3 has been identified as a valuable biomarker for patient prognosis and a potential target for CI.^26,27 Despite the growing attention that B7-H3 has received, there is a lack of systematic quantitative analysis of the output, current hotspots, and future study trends in B7-H3/CI on a global scale.

Bibliometric analysis employs statistical and mathematical methods to study literature’s quantity, quality, citations, and impact in a specific field.²⁸ Its objective is to reveal the scientific research capabilities of researchers, institutions, and countries based on quantitative support and to investigate research trends and hotspots by evaluating the metrological characteristics of papers.²⁹ In this study, we applied bibliometric analysis to outline the current status of B7-H3/CI and identified new directions for researchers in this field.

Materials and methods

Data source and search strategy

All publications on B7-H3/CI were retrieved from the Science Citation Index Expanded (SCIE) from the Web of Science Core Database (WOSCC) on November 20, 2022. The search strategies were TS = “B7-H3” and “immunotherapy” and “cancer.” The synonyms of the search terms and the wildcard “*” were used to expand the search scope and ensure the comprehensiveness of the search. The complete search terms are shown in “Supplementary Material S1”. The publications’ investigations ranged from 2012 to 2022. Document types were confined to “review” and “article.” After excluding non-English and non-main-topic literature, 555 records were downloaded as text files from the WOS (Figure 1).

Figure 1. Flowchart for screening publications in B7-H3/CI.

Data analysis and visualization

The Bibliometrix R package (version 4.2.1) was used to visualize the analysis of journals, countries/affiliations, and authors. The production dynamics, impact of journals, and history of direct citations were revealed using VOSviewer (version 1.6.18), facilitating the construction of a keyword co-occurrence analysis (frequency >10) and the citation network of institutions. An online platform (http://bibliometric.com) displays the cooperation networks between researchers and countries.

Results

The trend of global publications and citations

The number of publications (Np) increased from 2012 to 2022, with a notable spike from 2018 to 2022 (Figure 2a). Microsoft Excel 2019 was used to build a polynomial regression model to predict the Np in 2023. The model’s formula and R² were y = 0.7646 × 2–0.5566 x +18.352 and 0.9214, respectively, which indicated a reliable predictive performance. Based on the fitted curve, we estimated that Np for the entire year 2022 could be approximately 105, and it may increase to approximately 120 in 2023.

Figure 2. (a) annual output and polynomial fitting curve of publications in B7-H3/CI. (b) the yearly average number of citations in B7-H3/CI.

Papers published in 2015 and 2018 had a crucial scholarly impact, with average citations peaking at approximately 25 and 18, respectively, in two years (Figure 2b). As presented in Table 1, the top five articles in terms of total citations (TC) were TOPALIAN (2015), WEI (2018), MAHONEY (2015), GREEN (2012), and CHAUVIN (2015). Higher quality and lower NP contributed to the highest average annual citations in 2015. However, since 2018, the average number of citations has decreased, possibly due to the deferred citations in recent studies.

Table 1. The top 10 global cited papers related to B7-H3/CI based on total citations.

Paper	DOI	Total Citations	TC per Year	Normalized TC
TOPALIAN SL, 2015, CANCER CELL	10.1016/j.ccell.2015.03.001	2454	306.75	14.26
WEI SC, 2018, CANCER DISCOV	10.1158/2159–8290.CD-18-0367	1357	271.40	18.72
MAHONEY KM, 2015, NAT REV DRUG DISCOV	10.1038/nrd4591	830	103.75	4.82
GREEN MR, 2012, CLIN CANCER RES	10.1158/1078–0432.CCR-11-1942	474	43.09	6.56
CHAUVIN JM, 2015, J CLIN INVEST	10.1172/JCI80445	431	53.88	2.50
QIN S, 2019, MOL CANCER	10.1186/s12943-019-1091-2	427	106.75	10.54
MARIN-ACEVEDO JA, 2018, J HEMATOL ONCOL	10.1186/s13045-018-0582-8	407	81.40	5.62
WANG X, 2016, ONCOTARGETS THER	10.2147/OTT.S105862	398	56.86	5.56
SCHILDBERG FA, 2016, IMMUNITY	10.1016/j.immuni.2016.05.002	334	47.71	4.66
LOU YY, 2016, CLIN CANCER RES	10.1158/1078–0432.CCR-15-1434	262	37.43	3.66

Analysis of journals

All the papers, including 401 articles and 144 reviews, were published in 233 journals. Table 2 shows that the most productive journal was Frontiers in Immunology (n = 29), followed by Frontiers in Oncology (n = 23). The impact of journals was measured using TC and H-index indicators. Cancer Cell had the highest TC, with 2639 citations (Figure 3a), while Clinical Cancer Research was the most influential journal, according to the H-index (Figure 3b). Figure 3c shows that the top 10 journals cumulatively published 167 papers, accounting for approximately 30.09% of the total publications. The dynamics of the cumulative NP in the top 10 journals are shown in Figure 3d.

Figure 3. (a) the top 10 influential journals measured by TC. (b) the top 10 influential journals measured by H-index. (c) the top 10 productive journals. (d) the dynamics of the cumulative number of papers of the top 10 journals in B7-H3/CI.

Table 2. The top 10 productive journals related to B7-H3/CI.

Rank	Journals	Articles	IF(2021)	Partition(2021)	Countries
1	FRONTIERS IN IMMUNOLOGY	29	8.786	Q1	Switzerland
2	FRONTIERS IN ONCOLOGY	23	5.738	Q2	Switzerland
3	CANCER IMMUNOLOGY RESEARCH	19	12.020	Q1	USA
4	CLINICAL CANCER RESEARCH	19	13.801	Q1	USA
5	ONCOIMMUNOLOGY	17	7.723	Q1	USA
6	JOURNAL FOR IMMUNOTHERAPY OF CANCER	16	12.469	Q1	England
7	CANCER IMMUNOLOGY IMMUNOTHERAPY	13	6.630	Q1	USA
8	CANCERS	12	6.575	Q1	Switzerland
9	INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES	11	6.208	Q1	Switzerland
10	NATURE COMMUNICATIONS	8	17.674	Q1	England

Analysis of authors

The dataset involved 3743 authors, with the top 10 prolific authors coming from China and the USA, especially from Sichuan University West China Hosp. Zang XX showed apparent advantages in terms of NP, H-index, and TC, indicating a significant influence on B7-H3/CI (Table 3). Additionally, Zang began publishing relevant research as early as 2012, whereas half of the authors did not do so until 2017, with most papers published in 2019 (Figure 4a). In terms of author collaboration, Tong AP, Zhou LX, and Guo G had the strongest links (Figure 4b).

Figure 4. (a) the top 10 authors’ production over time in B7-H3/CI. (b) the top 20 authors’ cooperative network (each node corresponds to an author, the node’s size corresponds to the NP of the author, the line between authors represents a collaborative relationship, and the thickness of the line corresponds to the intensity of cooperation). (c) the trends in NP of top 5 productive institutions over time. (d) the citation network of 50 institutions.

Table 3. The top 10 productive authors related to B7-H3/CI.

Rank	Authors	Np	H-index	TC	Affiliations	Countries
1	ZANG XX	14	9	750	Montefiore Med Ctr, Albert Einstein Coll Med	USA
2	FERRONE S	13	9	476	Harvard Med Sch, Dept Orthopaed Surg	USA
3	TONG AP	13	9	265	Sichuan Univ, West China Hosp	China
4	ZHOU LX	11	8	239	Sichuan Univ, West China Hosp	China
5	GUO G	10	7	222	Third Mil Med Univ, South West Hosp	China
6	LIU Y	10	5	23	Zunyi Med Univ, Sch Stomatol	China
7	TANG X	10	9	253	Sichuan Univ, West China Hosp	China
8	WANG L	10	8	480	Mayo Clin, Div Hematol & Oncol	USA
9	ZHANG ZL	10	8	233	Binzhou Med Univ, Sch Clin Med	China
10	CHEN LP	9	8	489	Texas Childrens Hosp, Baylor Coll Med	USA

Analysis of countries/regions and institutions

We analyzed 818 institutions in this study. Table 4 lists the top 10 institutions in Np, six of which are from China. The top five institutions were Soochow University, Sichuan University, Fudan University, the University of Texas MD, Anderson Canc Ctr, and the Albert Einstein Coll Med. Figure 4c shows the trends in Np of the top five institutions. Among these, Soochow University ranked first in NP, while Sichuan University was the latest to start but the fastest to develop. The citation links between the 50 institutions publishing no fewer than five papers formed the citation network shown in Figure 4d.

Table 4. The top 10 productive countries/regions and institutions related to B7-H3/CI.

Rank	Countries	NP	TC	AC	Affiliation	NP
1	CHINA	221	5050	23.82	SOOCHOW UNIV(CHINA)	57
2	USA	213	13972	79.84	SICHUAN UNIV(CHINA)	51
3	JAPAN	33	572	22.88	FUDAN UNIV(CHINA)	41
4	GERMANY	31	318	13.25	UNIV TEXAS MD ANDERSON CANC CTR(USA)	41
5	ITALY	25	303	16.83	ALBERT EINSTEIN COLL MED(USA)	40
6	KREA	18	144	14.40	SUN YAT SEN UNIV(CHINA)	38
7	UK	17	762	76.20	CENT SOUTH UNIV(CHINA)	31
8	SPAIN	17	218	15.00	HARVARD MED SCH(USA)	30
9	CANADA	17	269	33.63	TABRIZ UNIV MED SCI(IRAN)	29
10	IRAN	12	235	19.58	CAPITAL MED UNIV(CHINA)	27

These papers were distributed across 45 countries/regions, with the USA and China being the major publication countries (Figure 5a). There were 44 multi-country publications (MCP) in the USA and 31 in China (Figure 5b). Among the top 10 relevant countries, Iran (50%) and Spain (60%) had a high proportion of MCP (Figure 5b). China surpassed the USA in 2020, as shown in Figure 5c. Figure 5d shows a map of the cooperation between the counties. The USA has cooperative relations with many countries, especially in maintaining close ties with China.

Figure 5. (a) Distribution of documents from different countries in B7-H3/CI. (b) the publications’ partnership of the top 10 countries in B7-H3/CI. (c) the trend in the number of papers from the top 10 countries. (d) the cooperative network of countries (the links between countries/regions indicate the number of cooperation).

Analysis of historical cited paper in B7-H3/CI

Historiographic analysis was used to identify classic papers in this field (Figure 6). The Local citation score (LCS) represents the number of citations of a paper in the downloaded dataset, whereas the global citation score (GCS) refers to the number of citations of an article cited by all papers in WoS. The LCS and GCS are indicators of the research quality of classic articles. The year 2017 (5) had the most publications in classical papers. The earliest paper, published in 2012, reported that higher expression of B7-H3 in hepatocellular carcinoma predicted poor clinicopathological characteristics and outcomes.³⁰ In 2013, Wang et al. demonstrated that B7-H3 accelerates the metastasis of osteosarcoma cells by upregulating matrix metalloproteinase-2.³¹ In 2014, a retrospective study found that high B7-H3 expression caused metastatic nodes in primary urothelial carcinoma of the bladder.³² In 2015 and 2017, two studies showed that B7-H3 is a prognostic factor for poor survival in lung cancer patients.^33,34 Another study in 2017 showed that the downregulation of B7-H3 enhanced the function of cytotoxic lymphocytes to inhibit tumor growth.³⁵ In 2018, a paper published in Clinical Cancer Research indicated that B7-H3 could avoid immune surveillance and that an inhibitor of B7-H3 combined with ICIs was a promising therapy for patients expressing B7-H3.³⁶ In 2019, two studies found that B7-H3 could be an exciting target for treating chimeric antigen receptor T cell (CAR-T) pediatric and pancreatic cancer.^37,38 Additional details are provided in Table 5.

Figure 6. History direct citation network in B7-H3/CI (each node corresponds to a paper, and the lines between the nodes represent the citation relationship).

Table 5. The papers of historical direct citation network related to B7-H3/CI.

NO.	Title	Journal	First author	Year	LCS	GCS
1	B7-H3 is expressed in human hepatocellular carcinoma and is associated with tumor aggressiveness and postoperative recurrence	Cancer Immuno Immun	Sun,TW	2012	31	78
2	B7-H3 is Overexpressed in Patients Suffering Osteosarcoma and Associated with Tumor Aggressiveness and Metastasis	Plos One	Wang, L	2013	30	97
3	HHLA2 is a member of the B7 family and inhibits human CD4 and CD8 T-cell function	P Natl Acad Sci USA	Zhao, RH	2013	25	114
4	B7-H3-mediated tumor immunology: Friend or foe?	Int J Cancer	Wang, L	2014	38	96
5	Association of T-cell co-regulatory protein expression with clinical outcomes following radical cystectomy for urothelial carcinoma of the bladder	Ejso	Xylinas, E	2014	20	122
6	Immune Checkpoint Blockade: A Common Denominator Approach to Cancer Therapy	Cancer Cell	Topalian, SL	2015	40	2454
7	B7-H1 and B7-H3 are independent predictors of poor prognosis in patients with non-small cell lung cancer	Oncotarget	Mao, YX	2015	20	87
8	Molecular Pathways: Targeting B7-H3 (CD276) for Human Cancer Immunotherapy	Clin Cancer Res	Picarda, E	2016	94	254
9	Coinhibitory Pathways in the B7-CD28 Ligand-Receptor Family	Immunity	Schildberg, FA	2016	20	334
10	Tumor B7-H3 (CD276) expression and smoking history in relation to lung adenocarcinoma prognosis	Lung Cancer	Inamura, K	2017	26	62
11	Inhibition of the B7-H3 immune checkpoint limits tumor growth by enhancing cytotoxic lymphocyte function	Cell Res	Lee, YH	2017	67	160
12	B7-H3 Expression in NSCLC and Its Association with B7-H4, PD-L1 and Tumor-Infiltrating Lymphocytes	Clin Cancer Res	Altan, M	2017	37	68
13	New B7 Family Checkpoints in Human Cancers	Mol Cancer Ther	Ni, L	2017	36	128
14	The third group of the B7-CD28 immune checkpoint family: HHLA2, TMIGD2, B7×, and B7-H3	Immunol Rev	Janakiram, M	2017	33	134
15	Next generation of immune checkpoint therapy in cancer: new developments and challenges	J Hematol Oncol	Marin-Acevedo, JA	2018	20	407
16	B7-H3 negatively modulates CTL-mediated cancer immunity	Clin Cancer Res	Yonesaka, K	2018	33	65
17	Antitumor Responses in the Absence of Toxicity in Solid Tumors by Targeting B7-H3 via Chimeric Antigen Receptor T Cells	Cancer Cell	Du, HW	2019	55	185
18	CAR T Cells Targeting B7-H3, a Pan-Cancer Antigen, Demonstrate Potent Preclinical Activity Against Pediatric Solid Tumors and Brain Tumors	Clin Cancer Res	Majzner, RG	2019	45	226
19	B7-H3 as a Novel CAR-T Therapeutic Target for Glioblastoma	Mol Ther-Oncolytics	Tang, X	2019	27	77
20	B7-H3, a checkpoint molecule, as a target for cancer immunotherapy	Int J Biol Sci	Yang, S	2020	22	84

Analysis of high-frequency keywords

In this study, 1324 author keywords and 1115 keywords plus were collected from the downloaded documents. Cloud maps of the hot words with the top 50 frequencies are shown in Figure 7a,b. After excluding search terms, the most common words for the author keywords were “immune checkpoint,” “PD-L1,” “prognosis,” “tumor microenvironment,” “PD-1,” etc. The most popular words for keywords plus were “expression,” “co-stimulatory molecule,” “activation,” “T-cell,” and “survival.”

Figure 7. (a) Word cloud of top 50 authors’ keywords in B7-H3/CI. (b) Word cloud of top 50 keywords plus in B7-H3/CI. (c) the cluster analysis of 122 keywords (frequency ≥10) in B7-H3/CI (the size of the node suggests the frequency of the keywords, and the thickness of the line between keywords indicates the total link strength). (d) trends in keywords (frequency ≥10) over time in B7-H3/CI.

We conducted a co-occurrence analysis of all keywords and created a network visualization, as shown in Figure 7c. A total of 122 words with more than 10 co-occurrences were classified into four clusters. Cluster 1 (Red, 48 items) was the largest one, of which “immunotherapy” showed the maximum total link strength (1229), followed by “expression” (1001). In cluster 2 (Green, 31 items), the primary keyword was “co-stimulatory molecule” (689). For cluster 3 (blue, 26 items) and cluster 4 (yellow, 17 items), the domain keywords were “B7 family” (443) and “PD-L1” (469) respectively.

Analysis of keyword trends

As shown in Figure 7d, an overlay visualization was constructed to predict the future direction of B7-H3/CI. According to the year of appearance and frequency of publication, the VOS viewer matched different colors for 122 words. Over time, the boxes transitioned from blue to yellow, indicating the emergence of new keywords in recent years. This shift in color suggests that “chimeric antigen receptor” (2020.54), “pathways” (2020.47), and “targeting B7-H3” (2021.08) might be the latest areas of interest for research.

Discussion

Bibliometrics is a rapidly developing field with broad applications across various domains. It focuses on the literature as the research object and helps researchers quickly locate research hotspots and track research trends in their respective fields by extracting the quantitative features of the literature for visualization. Based on bibliometric analysis, this study detailed the current state of B7-H3/CI research, visually described the most influential countries, institutions, journals, and authors in the field, and predicted that “chimeric antigen receptors (CARs),” “pathways,” and “targeting B7-H3” may be a new research hotspot. From 2012 to 2022, the annual Np of B7-H3/CI steadily increased and has not yet reached its peak, which has enormous research potential in the future.

Our study showed that Frontiers in Immunology attracted the most manuscripts from this field and was a notable domain journal for publications on B7-H3/CI. China outstripped the USA in Np, but its TC was less than half that of the USA, indicating that American papers had higher quality and scholarly impact. First-class universities and academic institutions have played important roles in augmenting national academic influence. Six of the top 10 prolific institutions came from China, and these institutions were among the top universities located in the economically developed regions of China, which could explain why China has the largest NP. Regarding author analysis, Zang XX from Montefiore Med Ctr and Albert Einstein Coll Med published the most papers on B7-H3/CI and had the highest TC. Regarding the impact of articles, the most cited paper was authored by Topalian.

The top globally cited publications and historical citation networks reflect the general development of B7-H3/CI. Since 2012, several studies have shown that B7-H3 is highly expressed in multiple solid tumors, such as hepatocellular carcinoma, osteosarcoma, and non-small cell lung cancer, contributing to tumor progression and poor outcomes.^30,31,33 Exploration of the prognostic value of B7-H3 is one of the current research hotspots. In 2018, Kimio found that B7-H3 blockade increased the infiltration of CD8+ T cells and recovered their effector function, proving that a combination of anti-PD-1 and B7-H3 blockade was a promising treatment to improve immunotherapy efficiency in patients with high B7-H3-expressing.³⁶ This landmark finding fueled researchers’ enthusiasm for the clinical translation of B7-H3 blocking. However, the dual blockade of B7-H3 and PD-1 showed worse response rates in melanoma patients.³⁹

Trend analysis revealed that B7-H3 targeting could be a new research direction. CAR-T therapy uses CAR-modified T cells to recognize and attack cancer cells that express a specific antigen on their surface.⁴⁰ This study highlights the use of CAR-T cells targeting B7-H3, which has shown great promise in recent years compared to delivering CAR-T cells to atypical teratoid/rhabdoid and pediatric brain tumors.^41,42 Seattle Children’s Hospital released preliminary first-in-human results (NCT04483778, STRIVE-02) on the use of CAR-T cells targeting B7-H3 in children and adolescents with relapsed or refractory solids. No dose-limiting toxicities were observed. After a single infusion, only three (33%) patients achieved stable disease, and the median survival time of CAR-T cells in the patients’ peripheral blood was 28 days. One patient received a second CAR-T infusion (1 × 106 CAR-T/kg), which resulted in a transient elevation of liver enzymes (grade 4), and the patient was assessed by PET/CT imaging as having a partial metabolic response 28 days after treatment.⁴³ Although CAR-T cells targeting B7-H3 have shown good efficacy and safety, constructing optimal B7-H3 CARs and exploring efficient routes of administration remains challenging.

Research on CAR-T cell therapy is currently the most extensive, and the early success of MGC018 and DS-7300a as B7-H3 blockade antibody – drug conjugates has accelerated the launch of clinical trials (NCT03729596, NCT05280470). A bispecific antibody (MDG009) targets CD3 and B7-H3 on T cells, and its safety and efficacy have been investigated in NCT03406949. B7-H3 blockade via antibody-dependent cellular cytotoxicity (NCT02982941, NCT02923180, and NCT02381314) and radioimmunotherapy (NCT04167618 and NCT04743661) are actively underway. Different types of antibodies and CAR-T cell therapies have reached the clinical trial stage (Supplementary Table S1), demonstrating the current focus on targeting B7-H3 in CI. However, the cost and toxicity of these therapies remain real concerns and may prevent their application in more sensitive populations.

B7-H3 is immunosuppressive molecule, involved in tumor immune escape as well as B7-H1. B7-H1 inhibits T cell activation by binding to the PD-1 receptor, helping tumor cells escape immune attack. B7-H3 inhibits the activity T cell⁴⁴ and NK cells,¹⁹ and promote regulatory T cell responses.⁴⁵ These immunosuppressive effects will be modulated, and anti-tumor immune responses will be enhanced when blocking or targeting B7-H3. Additionally, B7-H3 is highly expressed in a variety of tumor cells, and this selective expression pattern also makes it a potential target for cancer-specific immunotherapy, reducing nonspecific effects on normal tissues. Although the success of PD-1/PD-L1 immunotherapy may not be directly extended to B7-H3, early clinical studies have demonstrated the effects of B7-H3 targeting. B7-H3 deserves attention as a potential target for immunotherapy, but further studies are needed to fully evaluate its efficacy, safety, and combination with other therapies.

At present, the receptor for B7-H3 has not been identified, which hinders the clinical application of B7-H3-based CI. Post-translational modifications refer to further chemical modifications of a protein after translation that can alter its function or stability.⁴⁶ However, few PTMs of B7-H3 have been reported in previous studies, thus presenting a new approach for targeting B7-H3. The expression of B7-H3 is heterogeneous, and its role in tumors and autoimmune diseases varies significantly. However, the exact reasons for these differences remain unclear. Variable splicing is a crucial mechanism for transcriptional regulation that could potentially shed light on this issue, but further research is required to corroborate this hypothesis. To better understand tumorigenesis and CI from a cellular biology perspective, investigation of B7-H3-mediated pathways of tumorigenic molecular mechanisms is a future research direction.

Our study had some limitations. Research on B7-H3 is a very new field, so the amount of relevant literature may be limited. However, this study on B7-H3 has great clinical translation significance, related researches have entered the clinical trial stage, and the number of related literatures is also rapidly accumulating. We only retrieved English publication data from the SCIE of the WoSCC because English is the main language used in the literature, and the WoSCC has vast and high-quality literature coverage. Moreover, the analysis software of bibliometrics has faced challenges in analyzing literature sourced from various databases and containing multiple languages. Additionally, IF and TC did not adequately represent the academic value of an article because papers from a research team specializing in the field may also be authoritative. Finally, we may neglect newly published articles that have a significant impact but fewer citations.

In conclusion, bibliometric analysis showed that research on B7-H3/CI is rapidly developing, and NP will continue to increase. China published the maximum number of NP in this domain, and the USA has considerable authority on this theme, owing to the highest impact of publications. CAR-T cell targeting of B7-H3” may be a new research trend in the future.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The raw data supporting the conclusions of this article will be made available by the authors without undue reservation.

Supplementary data

Supplemental data for this article can be accessed on the publisher’s website at https://doi.org/10.1080/21645515.2023.2246498.

Additional information

Funding

This study was supported by three grants: 1. CSCO Pilotage Oncology Research Foundation [Y2019-AZZD-0471] 2. Xisike Hengrui Clinical Oncology Research Foundation [Y-HR2018-185] 3. Qingdao traditional Chinese medicine science and technology project (2021-zyym29) 4. Qingdao Municipal key clinical specialty 2022-2024 (Wensheng Qiu).