scholarly journals Tumor Mutation Burden: A Predictive Biomarker for Gastric Cancer Immunotherapy

2020 ◽  
Author(s):  
Renshen Xiang ◽  
Tao Fu
Keyword(s):  
Gastric Cancer ◽  
T Cells ◽  
Clinical Decision Making ◽  
Immune Cell ◽  
Predictive Biomarker ◽  
Clinical Decision ◽  
Tumor Mutation Burden ◽  
Follicular Helper ◽  
Tumor Purity ◽  
Mutation Burden

Abstract Background: Few studies have focused on the underlying relationship between the prognosis of tumor mutation burden (TMB) and immune cell infiltration in gastric cancer (GC). This study aims to explore the relationship among TMB and various components in tumor microenvironment (TME). Methods: The transcription profiles and somatic mutation data of 375 tumor and 32 normal samples were obtained from TCGA. The specific mutation information was summarized and visualized with waterfall chart, then number of TMB per million bases of each GC sample was calculated. Immune/stromal scores and tumor purity were calculated by the ‘ESTIMATE’ package, and the fractions of 22 immune cells in each sample were evaluated by CIBERSORT algorithm. Finally, Lass regression analysis was utilized to generate a prognostic scoring signature with TCGA cohort as the training set, while GES84437 cohort as the validation set. Results: Higher TMB indicated favorable overall survival (OS, P = 0.043)，better disease specific survival (P = 0.029), and longer progression free interval (P = 0.004). TMB was positively correlated with MSI and tumor purity, while negatively associated with immune/stromal scores. Moreover, TMBhigh group has lower T cells CD4 memory resting (P < 0.001) and T cells regulatory (P < 0.001), and more T cells CD4 memory activated (P < 0.001) and T cells follicular helper (P = 0.009). More importanly, the infiltration of dendritic cells activated predicted a worse OS, while T cells CD4 memory activated and T cells follicular helper meant a better OS. Finally, a nomogram combined TMB-related signature with clinicopathologic variables can successfully predict the OS with high accuracy and efficiency.Conclusion: TMB can effectively reveal the immune infiltration status in TME of GC, and might serve as a prognostic classifier for individualized treatment of clinical decision-making.

Co-mutations of KRAS/BRAF and TP53 or the high tumor mutation burden to predict survival in patients with biliary tract carcinoma.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16650-e16650
Author(s):  
Lingling Guo ◽  
Xiaoxia Kou ◽  
Panpan Song ◽  
Xiaoyu Zhang ◽  
Hongjuan Zhang ◽  
...  
Keyword(s):  
Biliary Tract ◽  
Poor Prognosis ◽  
Clinical Decision Making ◽  
Clinical Decision ◽  
Biliary Tract Carcinoma ◽  
Rank Test ◽  
Braf Mutations ◽  
Tumor Mutation Burden ◽  
Synonymous Mutations ◽  
Mutation Burden

e16650 Background: Biliary tract carcinoma (BTC), including cholangiocarcinoma and gallbladder carcinoma, is the second most common type of hepatobiliary cancer. Patients with BTC always show poor prognosis, here we revealed the molecular landscape of BTC in the Chinese population and evaluated the role of different mutations in informing prognosis. Methods: Formalin-Fixed Paraffin-Embedded (FFPE) or freshly-sampled tumor tissues from 59 BTC patients were conducted next-generation sequencing of 620 genes related to oncogenesis. Tumor mutation burden (TMB) value represents the number of non-synonymous mutations per mega base pairs in each sample. Kaplan-Meier survival curves were generated and compared using the log-rank test. Results: Altogether, 59 patients have mutations mainly in TP53, Ras/Raf, PI3K, CDK signaling pathways and SWI/SNF complex. The most frequently mutated gene was TP53(53%), followed by KRAS(23%), ARID1A(17%), ATM(12%), CDKN2A(10%), SMAD4(8%), BRCA2(8%), STK11(7%), BRAF(5%), IDH1(5%) and FGFR3 (3%). Noticeably, only one patient with FGFR2 fusion was detected. The Median TMB of these patients is 2.80 Muts/Mbp (0-36.52 Muts/Mbp). Existing data showed that KRAS/BRAF alterations were associated with a worse overall survival (OS) (median OS 166d vs. 294d, p= 0.063). Further analysis indicated that RAS/BRAF mutations were often co-current with TP53 alternations. And patients with coaltered RAS/BRAF and TP53 demonstrated the worst prognosis (media OS 123d vs. 294d, p= 0.087). In addition, a higher TMB ( > 2.80 Muts/Mb) was also associated with a worse survival (median OS 174d vs. 355d, p= 0.085). Conclusions: We identified KRAS/BRAF, or co-mutations with TP53 and high TMB could predict poor prognosis in BTC patients. These findings will be useful for clinical decision making in patients with refractory biliary tract cancer and for risk stratification of patients in future clinical studies.

Tumor mutation burden and immune microenvironment analysis of urothelial carcinoma.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 494-494
Author(s):  
Yuanyuan Jia ◽  
Ning He ◽  
Yadong Yang ◽  
Yuliang Huang ◽  
Xiaoyu Zhang ◽  
...  
Keyword(s):  
T Cells ◽  
Urothelial Carcinoma ◽  
Cd8 T Cells ◽  
Immune Cell ◽  
Immune Therapy ◽  
Genetic Alterations ◽  
Rank Test ◽  
Immune Microenvironment ◽  
Tumor Mutation Burden ◽  
Mutation Burden

494 Background: Tumor mutation burden (TMB) has been established as a biomarker for response to immune therapy and prognosis in various cancers. However, the correlation between TMB and immune microenvironment remains unwell studied, especially in urothelial carcinoma. This study was aimed to investigate the relationship between TMB and other immunotherapy related biomarkers, including genetic alterations, APOBEC signature, microsatellite instability (MSI), PD-L1 expression and immune cell infiltration in urothelial carcinoma. Methods: 131 patients with urothelial carcinoma admitted from October 2018 to May 2020 were included. Total DNA was isolated from FFPE or fresh tissues. Mutation profiles, APOBEC signature and MSI scores were obtained by next-generation sequencing based a 642 cancer genes panel assay. PD-L1 expression, CD8+ T-cells and tumor-infiltrating lymphocytes density were evaluated by immunohistochemistry. The correlation was analyzed by Wilcoxon signed-rank test. Results: The mutation landscape showed that TP53 mutation is the most common alterations (n = 64/131, 48.9%), followed by KMT2D alterations (n = 49/131, 37.4%), KDM6A mutations (n = 42/131, 32.1%), MUC17 mutations (n = 42/131, 32.1%). The median TMB was 5.06 Muts/Mb (0-118 Muts/Mb). 2 of 131 patients showed MSI-H, who exhibited a much higher TMB (41, 118 Muts/Mb). Further analysis showed that TMB in the patients with certain gene mutations (such as TP53, KMT2D, KDM6A and MUC17) was significantly higher than those wild type ones (p < 0.05). Meanwhile, the high APOBEC-enrichment group has a higher TMB than the low APOBEC-enrichment group (p = 0.045). Furthermore,we observed that the patients with a higher PD-L1 expression (n = 28/131, 21.4%, at a combined positive score cut-off value of 10) also showed a significantly higher TMB (p = 0.016), and TMB in the patients with higher density of CD8+ T-cells (n = 42/131, 32.1%, at a cut-off value of 5%) was also significantly higher than that of the group with lower density of CD8+ T-cells (p = 0.039). Conclusions: This study provides new insights into the correlation between the TMB and the immune microenvironment in urothelial carcinoma. The result may be a reference to immunotherapy.

Increased neutrophil infiltration and lower prevalence of tumor mutation burden and microsatellite instability are hallmarks of RAS mutant colorectal cancers.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 3563-3563
Author(s):  
Emil Lou ◽  
Yasmine Baca ◽  
Joanne Xiu ◽  
Andrew Nelson ◽  
Subbaya Subramanian ◽  
...  
Keyword(s):  
T Cells ◽  
B Cells ◽  
Cd8 T Cells ◽  
Immune Cell ◽  
Neutrophil Infiltration ◽  
Cell Fraction ◽  
Colorectal Cancers ◽  
Tumor Mutation Burden ◽  
Immune Infiltration ◽  
Mutation Burden

3563 Background: The tumor microenvironment (TME) of colorectal cancers (CRC) is modulated by oncogenic drivers such as KRAS. The TME comprises a broad landscape of immune infiltration. How tumor genomics associates with the immune cell landscape is less known. We aim to characterize immune cell types in RAS wild-type (WT) and mutant (MT) CRC, and to examine the prevalence of immuno-oncologic (IO) biomarkers (e.g. tumor mutation burden (TMB), PD-L1, MSI-H/dMMR) in these tumors. We performed genomic and transcriptomic analysis to confirm associations of mutant RAS with immune infiltration of the TME conducive to metastasis vs. potential response to immunotherapies. Methods: A total of 7,801 CRC were analyzed using next-generation sequencing on DNA (NextSeq, 592 Genes and WES, NovaSEQ), RNA (NovaSeq, whole transcriptome equencing) and IHC (Caris Life Sciences, Phoenix, AZ). MSI/MMR was tested by FA, IHC and NGS. TMB-H was based on a cut-off of > 10 mutations per MB). Immune cell fraction was calculated by QuantiSeq (Finotello 2019, Genome Medicine). Significance was determined by X2 and Fisher-Exact and p adjusted for multiple comparisons (q) was <0.05. Results: Mutant KRAS was seen in 48% of mCRC tumors; NRAS in 3.7%, HRAS in 0.1%. The distribution was similar in patients < or >= than 50 yrs. In MSS tumors, there was a significantly higher neutrophil infiltration in KRAS MT (median cell fraction 6.6% vs. 5.9%) and NRAS MT (6.9%) overall and also when individual codons were studied. B cells, M2 macrophages, CD8+ T cells, dendritic cells and fibroblasts were lower in KRAS mutant tumors; B cells and M1 macrophages are lower in NRAS (q<0.05). dMMR/MSI-H was significantly more prevalent in RAS WT (9.1%) than in KRAS (2.9%) or NRAS MT (1.8%) tumors, and highest in HRAS MT tumors (60%, q<0.05).TMB-H was more prevalent in RAS WT (11%) than KRAS (5.8%) or NRAS (5.1%) MT, and highest in HRAS MT tumors (70%, all q<0.05). In MSS tumors, KRAS MT tumors showed more TMB-H than WT (3.1% vs. 2.1%, q<0.05), especially in KRAS non 12/13/61 mutations (5.5%, vs. 2.1%, q<0.05) and G12C (4.4%, p<0.05). PD-L1 expression was studied: in MSS tumors, KRAS-G12D (10.4%) and G13 MT (11.8%) showed higher mutation rates than RAS WT tumors (q<0.05). Conclusions: KRAS & NRAS mutations are associated with increased neutrophil abundance, with codon specific differences, while HRAS shows no difference. Overall CD8+ T cells and B cells are less abundant in KRAS & NRAS mutants; substantial variability was seen amongst different protein changes. RAS mutations were more prevalent overall than generally reported, but did not vary by age. These results demonstrate significant differences in the TME of RAS mutant CRC that identify variable susceptibilities to immuno-oncologic agents, and provide further detailed characterization of heterogeneity between RAS variants, at the molecular as well as immunogenic levels.

scholarly journals Comprehensive analysis of tumor mutation burden and immune microenvironment in gastric cancer

2021 ◽  
Vol 41 (2) ◽  
Author(s):  
Jie Yu ◽  
QianYun Zhang ◽  
MengChuan Wang ◽  
SiJia Liang ◽  
HongYun Huang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
T Cells ◽  
Immune Cells ◽  
Survival Outcome ◽  
Prognostic Role ◽  
High Group ◽  
Tumor Mutation Burden ◽  
Immune Genes ◽  
Mutation Burden

Abstract Tumor mutation burden (TMB) was a promising marker for immunotherapy. We aimed to investigate the prognostic role of TMB and its relationship with immune cells infiltration in gastric cancer (GC). We analyzed the mutation landscape of all GC cases and TMB of each GC patient was calculated and patients were divided into TMB-high and TMB-low group. Differentially expressed genes (DEGs) between the two groups were identified and pathway analysis was performed. The immune cells infiltration in each GC patient was evaluated and Kaplan–Meier analysis was performed to investigate the prognostic role of immune cells infiltration. At last, hub immune genes were identified and a TMB prognostic risk score (TMBPRS) was constructed to predict the survival outcome of GC patients. The relationships between mutants of hub immune genes and immune infiltration level in GC was investigated. We found higher TMB was correlated with better survival outcome and female patients, patients with T1-2 and N0 had higher TMB score. Altogether 816 DEGs were harvested and pathway analysis demonstrated that patients in TMB-high group were associated with neuroactive ligand–receptor interaction, cAMP signaling pathway, calcium signaling pathway. The infiltration of activated CD4+ memory T cells, follicular helper T cells, resting NK cells, M0 and M1 macrophages and neutrophils in TMB-high group were higher compared than that in TMB-low group and high macrophage infiltration was correlated with inferior survival outcome of GC patients. Lastly, the TMBPRS was constructed and GC patients with high TMBPRS had poor prognosis.

Awareness and utilization of tumor mutation burden (TMB) as a biomarker for administration of immuno-oncology (I-O) therapeutics by practicing community oncologists in the United States (U.S.).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 2608-2608
Author(s):  
Kristin M. Zimmerman Savill ◽  
Marjorie E. Zettler ◽  
Bruce A. Feinberg ◽  
Yolaine Jeune-Smith ◽  
Ajeet Gajra
Keyword(s):  
Solid Tumors ◽  
Tumor Cells ◽  
Clinical Decision Making ◽  
Objective Response ◽  
Predictive Biomarker ◽  
Clinical Decision ◽  
The United States ◽  
Mutation Burden ◽  
Definition Of ◽  
The U.S

2608 Background: TMB, a measurement of the number of mutations carried by tumor cells, is emerging as a biomarker for the identification of patients who may benefit from certain I-O-based therapies. TMB-high (TMB-H) tumors, defined by the detection of ≥10 mutations/megabase (mut/Mb) in tumor cells using a tissue-based assay such as the FoundationOneCDx (F1CDx) assay (Foundation Medicine, Inc.), may be more likely to respond to some I-O therapies. Higher neoantigen loads of TMB-H tumors have been proposed to contribute to increased responsiveness of TMB-H tumors to certain I-O therapeutics. Pembrolizumab was approved by the FDA on June 16, 2020 for the treatment of adult and pediatric patients with unresectable or metastatic TMB-H tumors, as determined by F1CDx, based on results from the KEYNOTE-158 trial (NCT02628067), which demonstrated that 50% of patients with TMB-H tumors had response durations of ≥24 months, with objective response rates in TMB-H vs. non-TMB-H patients of 29% and 6%, respectively (Marabelle et al, The Lancet Oncology, 2020). This survey-based study aimed to evaluate awareness and utilization of TMB as a biomarker for I-O therapeutics among practicing community oncologists in the U.S. Methods: Questions related to awareness and utilization of TMB as a biomarker for I-O therapeutics were developed by two medical oncologists (AG and BF) and presented to community oncologists in a web-based survey prior to virtual meetings held between October and November 2020. Descriptive statistics were used to analyze the results. Results: Of the 193 participating providers geographically distributed across the U.S., 15% reported being unaware of either the concept of TMB in I-O therapy or how to use the information clinically. 39% of these providers reported testing ≤25% of patients with advanced cancer for TMB, including 8% who do not test for TMB at all. Misconceptions regarding TMB identified among participating providers included the belief that high TMB is considered to be > 5 mut/Mb among 20% of providers, that TMB is essentially the same as MSI-high among 8% of providers, and that there are no therapies with FDA approval based on TMB among 15% of providers. Further, 37% of the participants did not identify pembrolizumab as an agent approved for the treatment of solid tumors based on TMB-H status. Conclusions: These findings demonstrate that there is a knowledge gap regarding the definition of TMB, testing for TMB, as well as implementation of TMB status in clinical decision making. Education directed towards community oncology providers regarding TMB and its use as a predictive biomarker for I-O therapy may improve its utilization and adoption in solid tumors to improve patient outcomes.

Response Predictors for Pembrolizumab in Advanced NSCLC beyond PD-L1 Expression

2019 ◽  
Vol 3 (2) ◽  
pp. 01-05
Author(s):  
Bakulesh Khamar
Keyword(s):  
Advanced Nsclc ◽  
Immune Cell ◽  
Predictive Biomarker ◽  
Current Status ◽  
Tumor Mutation Burden ◽  
Site Type ◽  
Response Predictors ◽  
Mutation Burden ◽  
Improved Outcome

Pembrolizumab has significantly improved outcome of advanced NSCLC. PD-L1 expression has limited utility as a prognostic and predictive biomarker. To improve this several other biomarkers have been evaluated. Useful amongst them are 1. Tumor specific biomarkers include tumor mutation burden, immune cell infiltration (phenotype, genotype, site, type), 2. Changes in cellular, cytokine in peripheral blood. The article provides review of the current status.

Correlation between peripheral CD8+PD-1+ T cells diversity, tumor mutation burden (TMB) and T cell clones with anti-PD-1 antibody treatment of lung cancer patients: TCR repertoire as a novel predictive biomarker.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e14041-e14041
Author(s):  
Seiji Matsumoto ◽  
Takaji Matsutani ◽  
Yoshiko Fujita ◽  
Kazutaka Kitaura ◽  
Yukio Nakamura ◽  
...  
Keyword(s):  
T Cells ◽  
Peripheral Blood ◽  
Predictive Biomarker ◽  
Shannon Index ◽  
Simpson Index ◽  
Tumor Mutation Burden ◽  
Repertoire Analysis ◽  
Mutation Burden ◽  
Tcr Repertoire ◽  
Tcr Diversity

e14041 Background: Anti-PD-1 antibodies (nivolumab) are effective in the treatment of many cancers. There is a demand for less invasive biomarkers. Peripheral and tumor CD8+PD-1+ T cells share neoantigen-specific T-cell receptors (TCRs), and are presumed to act as effector T cells with an antitumor effect at the tumor site. We analyzed the diversity in terms of TCR α and β repertoires on peripheral CD8+PD-1+ T cells, tumor mutation burden and examined the relationship between this diversity and therapeutic effect of nivolumab. Methods: This study used patients administered nivolumab after exhibiting no response to chemotherapy for recurrence following surgery. Peripheral blood mononuclear cells were collected from patients before administration of nivolumab. CD8+PD-1+ T cells were subjected to FACS sorting, NGS-based TCR repertoire analysis was performed by Repertoire Genesis Inc., and TCR diversity was evaluated statistically. This study was approved by the Ethical Committee of Hyogo College of Medicine. Results: Six of 12 patients responded to treatment. Upon comparing these responders (CR, PR) with non-responders (SD, PD), there were no differences in the proportion of PD-1+ in CD8+ T cells and the proportion of CD8+PD-1+ T cells in gated lymphocytes. TCR α diversity was significantly higher among responders than non-responders based on Shannon index, Simpson index and DE50 (P < 0.05, P < 0.05, P < 0.01, respectively). TCR β diversity was also significantly higher among responders than non-responders based on Shannon index, Simpson index and DE50 (all P < 0.01). Progression-free survival (PFS) was 371 days for responders and 148 days for non-responders. Overall survival (OS) was 633 days for responders and 308 days for non-responders, showing a significant difference between the groups. TCR repertoire was proportional to TMB. Clones found in multiple patients were more frequent in indel than in SNP. Conclusions: TCR repertoire analysis was performed on CD8+PD-1+ T cells in easily-obtainable peripheral blood before nivolumab treatment in patients with NSCLC, and nivolumab was observed to be effective in patients with high TCR diversity. This result indicates the TCR diversity of peripheral CD8+PD-1+ T cells is effective as a predictive biomarker for response to ICI therapy.

scholarly journals AEBP1 Predicts Clinical Prognosis and is Associated with Immunocyte Infiltration in Gastric Cancer

2021 ◽  
Author(s):  
Junsheng Deng ◽  
Ting Zhan ◽  
Xiaoli Chen ◽  
Yiyuan Wan ◽  
Mengge Chen ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
T Cells ◽  
Immune Cell ◽  
Progression Free Survival ◽  
Predictive Biomarker ◽  
Cell Infiltration ◽  
Gene Marker ◽  
Immune Cell Infiltration ◽  
Clinical Prognosis ◽  
The Relationship

Abstract AEBP1 is differentially expressed in various tumors. However, the correlation between AEBP1 and immune cell infiltration in gastric cancer remains unclear. Kaplan-Meier survival curves were used to evaluate the relationship between AEBP1 expression and overall survival and progression-free survival. The relationship between AEBP1 expression and infiltrating immune cells, and their corresponding gene marker sets was examined using the TIMER database.The expression of AEBP1 was lower in gastric cancer (GC) tumor tissues than in normal tissues (P < 0.05). High AEBP1 gene expression and high levels of AEBP1 gene methylation were correlated with high-grade malignant tumor and old TNM stage. In addition, in gastric cancer, there was a positive correlation between AEBP1 expression and immune infiltrating cells, including neutrophils, CD8 + T cells, and CD4 + T cells, as well as immune-related genes, including CD2, CD3D, and CD3E. Methylation sites such as cg00009293, cg08495088, cg12955216, cg10480062, cg06852744 and cg12978582 were positively correlated with low expression of AEBP1. AEBP1 may be a potential tumor suppressor gene in GC and a potential novel therapeutic target and predictive biomarker for GC. AEBP1 likely plays an important role in immune cell infiltration.

scholarly journals A gene expression signature of TREM2hi macrophages and γδ T cells predicts immunotherapy response

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Donghai Xiong ◽  
Yian Wang ◽  
Ming You
Keyword(s):  
T Cells ◽  
Clinical Decision Making ◽  
Immune Cell ◽  
Cell Subset ◽  
Γδ T Cells ◽  
Gene Expression Signature ◽  
Predictive Biomarkers ◽  
Clinical Decision ◽  
Gammadelta T Cells ◽  
Immune Cell Subsets

Abstract Identifying factors underlying resistance to immune checkpoint therapy (ICT) is still challenging. Most cancer patients do not respond to ICT and the availability of the predictive biomarkers is limited. Here, we re-analyze a publicly available single-cell RNA sequencing (scRNA-seq) dataset of melanoma samples of patients subjected to ICT and identify a subset of macrophages overexpressing TREM2 and a subset of gammadelta T cells that are both overrepresented in the non-responding tumors. In addition, the percentage of a B cell subset is significantly lower in the non-responders. The presence of these immune cell subtypes is corroborated in other publicly available scRNA-seq datasets. The analyses of bulk RNA-seq datasets of the melanoma samples identify and validate a signature - ImmuneCells.Sig - enriched with the genes characteristic of the above immune cell subsets to predict response to immunotherapy. ImmuneCells.Sig could represent a valuable tool for clinical decision making in patients receiving immunotherapy.

scholarly journals Development of an Immune-Related Gene Signature for Prognosis in Melanoma

2021 ◽  
Vol 10 ◽  
Author(s):  
Jia-An Zhang ◽  
Xu-Yue Zhou ◽  
Dan Huang ◽  
Chao Luan ◽  
Heng Gu ◽  
...  
Keyword(s):  
T Cells ◽  
Immune Cell ◽  
Treatment Method ◽  
Gene Signature ◽  
Cell Infiltration ◽  
Venn Diagram ◽  
Immune Cell Infiltration ◽  
Tumor Purity ◽  
New Treatment ◽  
Immune Related Genes

Melanoma remains a potentially deadly malignant tumor. The incidence of melanoma continues to rise. Immunotherapy has become a new treatment method and is widely used in a variety of tumors. Original melanoma data were downloaded from TCGA. ssGSEA was performed to classify them. GSVA software and the "hclust" package were used to analyze the data. The ESTIMATE algorithm screened DEGs. The edgeR package and Venn diagram identified valid immune-related genes. Univariate, LASSO and multivariate analyses were used to explore the hub genes. The "rms" package established the nomogram and calibrated the curve. Immune infiltration data were obtained from the TIMER database. Compared with that of samples in the high immune cell infiltration cluster, we found that the tumor purity of samples in the low immune cell infiltration cluster was higher. The immune score, ESTIMATE score and stromal score in the low immune cell infiltration cluster were lower. In the high immune cell infiltration cluster, the immune components were more abundant, while the tumor purity was lower. The expression levels of TIGIT, PDCD1, LAG3, HAVCR2, CTLA4 and the HLA family were also higher in the high immune cell infiltration cluster. Survival analysis showed that patients in the high immune cell infiltration cluster had shorter OS than patients in the low immune cell infiltration cluster. IGHV1-18, CXCL11, LTF, and HLA-DQB1 were identified as immune cell infiltration-related DEGs. The prognosis of melanoma was significantly negatively correlated with the infiltration of CD4+ T cells, CD8+ T cells, dendritic cells, neutrophils and macrophages. In this study, we identified immune-related melanoma core genes and relevant immune cell subtypes, which may be used in targeted therapy and immunotherapy of melanoma.

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