• Cancer
• HLA-G
• Immune checkpoint blockades
• Immunotherapy

• Humans
• HLA-G Antigens
• Neoplasms/therapy
• Biomarkers
• Immunotherapy
• Extracellular Vesicles/metabolism

• 2020YFC2008000 Key Technologies Research and Development Program

• Antigen presentation
• B2M
• Cancer immune evasion
• Cancer immunotherapy
• MHC-I
• TME

• Humans
• Histocompatibility Antigens Class I/genetics
• Histocompatibility Antigens Class I/metabolism
• Neoplasms/genetics
• Neoplasms/therapy
• Immunotherapy
• Cell Membrane/metabolism
• Tumor Microenvironment

• 81772710 National Natural Science Foundation of China
• 82172691 National Natural Science Foundation of China
• YKK19011 Nanjing Science and Technology Development Key Project

• Colorectal cancer
• HLA-G
• Prognosis
• meta-analysis

• Humans
• Prognosis
• HLA-G Antigens/genetics
• Biomarkers, Tumor/genetics
• Biomarkers, Tumor/metabolism
• Lymphatic Metastasis
• Colorectal Neoplasms/pathology

• HLA-G
• cancer
• human leukocyte antigen G
• meta – analysis
• tumors

• Colorectal cancer
• HLA-G
• Immune response
• Survival outcomes

• Humans
• HLA-G Antigens
• Prognosis
• Colorectal Neoplasms/diagnosis

• Università degli Studi di Genova

• Immune escape
• K-RAS
• MHC class I
• colorectal carcinoma
• extracellular matrix protein
• oncogene
• proteoglycan

• Animals
• Biglycan/genetics
• Biglycan/metabolism
• Colorectal Neoplasms/genetics
• Fibroblasts/metabolism
• Histocompatibility Antigens Class I/genetics
• Histocompatibility Antigens Class I/metabolism
• Humans
• Mice
• RNA, Messenger/metabolism
• Transfection

• HLA-G
• immune checkpoints
• tumors

• HLA-G
• KIR2DL4
• breast cancer
• immune microenvironment
• immunotherapy

• Breast Neoplasms/genetics
• Breast Neoplasms/immunology
• Breast Neoplasms/pathology
• Drug Resistance, Neoplasm/genetics
• Drug Resistance, Neoplasm/immunology
• Female
• HLA-G Antigens/genetics
• HLA-G Antigens/immunology
• Humans
• Killer Cells, Natural/immunology
• Receptors, KIR2DL4/genetics
• Receptors, KIR2DL4/immunology
• Tumor Microenvironment/genetics
• Tumor Microenvironment/immunology

• Cancer
• HLA-G
• ILT2
• autoimmunity
• checkpoint
• immunoediting
• polymorphisms
• therapy

• Animals
• Autoimmune Diseases/etiology
• Autoimmune Diseases/immunology
• Autoimmune Diseases/physiopathology
• HLA-G Antigens/genetics
• HLA-G Antigens/immunology
• Humans
• Immune Tolerance
• Killer Cells, Natural/immunology
• Mice
• Neoplasms/etiology
• Neoplasms/immunology
• Neoplasms/physiopathology
• Polymorphism, Genetic
• T-Lymphocytes/immunology

• Instituto de Salud Carlos III

The immune system recognizes and destroys cancer cells. However, cancer cells develop mechanisms to avoid detection by expressing cell surface proteins. Specific tumour cell surface proteins (e.g. HLA-G, PD-L1, CDX2) either alone or in combination with the relative presence of immune cells (CD3 and CD8 positive T-cells) in the tumour tissue may describe the cancer cells’ ability to escape eradication by the immune system. The aim was to investigate the prognostic value of immunohistochemical markers in patients with colon cancer.

We conducted a retrospective study including patients diagnosed with pT3 and pT4 colon cancers. Immunohistochemical staining with HLA-G, PD-L1, CDX2, CD3, and CD8 was performed on tissue samples with representation of the invasive margin. PD-L1 expression in tumour cells and immune cells was reported conjointly. The expression of CD3 and CD8 was reported as a merged score based on the expression of both markers in the invasive margin and the tumour centre. Subsequently, a combined marker score was established based on all of the markers. Each marker added one point to the score when unfavourable immunohistochemical features was present, and the score was categorized as low, intermediate or high depending on the number of unfavourable stains. Hazard ratios for recurrence, disease-free survival and mortality were calculated.

We included 188 patients undergoing colon cancer resections in 2011–2012. The median follow-up was 41.7 months, during which 41 (21.8%) patients had recurrence and 74 (39.4%) died. In multivariable regression analysis positive HLA-G expression (HR = 3.37, 95%CI [1.64–6.93]) was associated with higher recurrence rates, while a preserved CDX2 expression (HR = 0.23, 95%CI [0.06–0.85]) was associated with a lower risk of recurrence. An intermediate or high combined marker score was associated with increased recurrence rates (HR = 20.53, 95%CI [2.68–157.32] and HR = 7.56, 95%CI [1.06–54.16], respectively). Neither high expression of PD-L1 nor high CD3-CD8 score was significantly associated with recurrence rates. Patients with a high CD3-CD8 score had a significantly longer DFS and OS.

In tumour cells, expression of HLA-G and loss of CDX2 expression were associated with cancer recurrence. In addition, a combination of certain tumour tissue biomarkers was associated with colorectal cancer recurrence.

The online version contains supplementary material available at 10.1186/s12885-022-09169-0.

• CD3
• CD8
• CDX2
• Colon cancer
• Disease-free survival
• HLA-G
• Immunohistochemistry
• Overall survival
• PD-L1
• Time to recurrence

• +3142C/G
• 14 pb insertion/deletion
• Colorectal cancer
• HLA-G
• Polymorphism
• SNP

Immunotherapy has revolutionized therapeutic patterns of small cell lung cancer (SCLC). Human leukocyte antigen class II (HLA class II) is related to antitumor immunity. However, the implications of HLA class II in SCLC remain incompletely understood.

We investigated the expression patterns of HLA class II on tumor cells and tumor-infiltrating lymphocytes (TILs) by immunohistochemistry staining and its association with clinical parameters, immune markers, and recurrence-free survival (RFS) in 102 patients with stage I–III SCLC with radical surgery. Additionally, an HLA class II-based immune risk model was established by least absolute shrinkage and selection operator regression. With bioinformatics methods, we investigated HLA class II-related enrichment pathways and immune infiltration landscape in SCLC.

HLA class II on tumor cells and TILs was positively expressed in 9 (8.8%) and 45 (44.1%) patients with SCLC, respectively. HLA class II on TILs was negatively associated with lymph node metastasis and positively correlated with programmed death-ligand 1 (PD-L1) on TILs (p<0.001) and multiple immune markers (CD3, CD4, CD8, FOXP3; p<0.001). Lymph node metastasis (OR 0.314, 95% CI 0.118 to 0.838, p=0.021) and PD-L1 on TILs (OR 3.233, 95% CI 1.051 to 9.95, p=0.041) were independent predictive factors of HLA class II on TILs. HLA class II positivity on TILs prompted a longer RFS (40.2 months, 95% CI 31.7 to 48.7 vs 28.8 months, 95% CI 21.4 to 36.3, p=0.014). HLA class II on TILs, PD-L1 on TILs, CD4, and FOXP3 were enrolled in the immune risk model, which categorized patients into high-risk and low-risk groups and had better power for predicting the recurrence than tumor stage. Pathway enrichment analyses showed that patients with high HLA class II expression demonstrated signatures of transmembrane transportation, channel activity, and neuroactive ligand–receptor interaction. High-risk SCLC patients had a higher proportion of T follicular helper cells (p=0.034) and a lower proportion of activated memory CD4-positive T cells (p=0.040) and resting dendritic cells (p=0.045) versus low-risk patients.

HLA class II plays a crucial role in tumor immune microenvironment and recurrence prediction. This work demonstrates the prognostic and clinical values of HLA class II in patients with SCLC.

• antigen presentation
• immunohistochemistry
• lung neoplasms
• lymphocytes
• tumor microenvironment
• tumor-infiltrating

• HLA-G
• carcinoma
• clinical outcomes
• immunotherapy

Immune checkpoint inhibitors (ICIs) have become a promising immunotherapy for cancers. Human leukocyte antigen-G (HLA-G), a neoantigen, its biological functions and clinical relevance have been extensively investigated in malignancies, and early clinical trials with “anti-HLA-G strategy” are being launched for advance solid cancer immunotherapy. The mechanism of HLA-G as a new ICI is that HLA-G can bind immune cell bearing inhibitory receptors, the immunoglobulin-like transcript (ILT)-2 and ILT-4. HLA-G/ILT-2/-4 (HLA-G/ILTs) signaling can drive comprehensive immune suppression, promote tumor growth and disease progression. Though clinical benefits could be expected with application of HLA-G antibodies to blockade the HLA-G/ILTs signaling in solid cancer immunotherapy, major challenges with the diversity of HLA-G isoforms, HLA-G/ILTs binding specificity, intra- and inter-tumor heterogeneity of HLA-G, lack of isoform-specific antibodies and validated assay protocols, which could dramatically affect the clinical efficacy. Clinical benefits of HLA-G-targeted solid cancer immunotherapy may be fluctuated or even premature unless major challenges are addressed.

• HLA-G
• cancer immunotherapy
• immune checkpoint
• immune checkpoint inhibitor
• immunoglobulin-like transcript

The immune system plays an important role in protecting the body against malignancy. During cancer immunoediting, the immune system can recognize and keep checking the tumor cells by down-expression of some self-molecules or by increasing expression of some novel molecules. However, the microenvironment created in the course of cancer development hampers the immune ability to recognize and destroy the transforming cells. Human Leukocyte Antigen G (HLA-G) is emerging as immune checkpoint molecule produced more by cancer cells to weaken the immune response against them. HLA-G is a non-classical HLA class I molecule which is normally expressed in immune privileged tissues as a soluble or membrane-bound protein. HLA-G locus is highly polymorphic in the non-coding 3′ untranslated region (UTR) and in the 5′ upstream regulatory region (5′ URR). HLA-G expression is controlled by polymorphisms located in these regions, and several association studies between these polymorphic sites and disease predisposition, response to therapy, and/or HLA-G protein expression have been reported. Various polymorphisms are demonstrated to modulate its expression and this is increasingly finding more significance in cancer biology. This review focuses on the relevance of the HLA-G gene and its polymorphisms in cancer development. We highlight population genetics of HLA-G as evidence to espouse the need and importance of exploring potential utility of HLA-G in cancer diagnosis, prognosis and immunotherapy in the currently understudied African population.

• HLA-G
• ILT-2
• ILT-4
• PD-L1
• colorectal cancer
• prognosis

• HLA-G antigens
• cancer
• gastrointestinal
• meta-analysis
• prognosis

• Cancer immunobiology
• Human leukocyte antigen G
• melanomas
• systematic review

• HLA-G Antigens/genetics
• Humans
• Immunohistochemistry
• Melanoma/genetics
• Prognosis
• Uveal Neoplasms

• Human Leucocyte Antigen G
• ILT2/CD85j/LILRB1
• Natural Killer T cells
• immune regulation
• tolerogenic dendritic cells

Human leukocyte antigen-G (HLA-G) is a non-classical major histocompatibility complex class I (MHC I) molecule, and under physiological conditions, its expression is strictly restricted to the maternal–fetal interface and immune-privileged organs where HLA-G is expected to contribute to establishment and maintenance of immune tolerance. However, the expression of HLA-G has been found in various types of tumors, and the level of its expression frequently correlates with high-grade histology and poor prognosis, raising the possibility that it may play a negative role in tumor immunity. ILT2 and ILT4, present on a broad of immune cells, have been identified as the main receptors engaging HLA-G, and their interactions have been found to allow the conversion of effectors like NK cells and T cells to anergic or unresponsive state, activated DCs to tolerogenic state, and to drive the differentiation of T cells toward suppressive phenotype. Therefore, tumors can employ HLA-G to modulate the phenotype and function of immune cells, allowing them to escape immune attack. In this review, we discuss the mechanism underlying HLA-G expression and function, its role played in each step of the tumor-immunity cycle, as well as the potential to target it for therapeutic benefit.

• function
• human leukocyte antigen-G
• immune cells
• phenotype
• tumor

• HLA-G
• antibody
• colorectal cancer
• esophageal cancer
• heterogeneity
• isoform
• tumor

• HLA-G
• hematopoietic tumors
• immune checkpoint
• immunotherapy
• solid tumors

• Animals
• Antibodies, Monoclonal/therapeutic use
• Antigens, Neoplasm/immunology
• Antigens, Neoplasm/metabolism
• Antineoplastic Agents, Immunological/therapeutic use
• HLA-G Antigens/immunology
• HLA-G Antigens/metabolism
• Humans
• Immunotherapy, Adoptive
• Neoplasms/immunology
• Neoplasms/metabolism
• Neoplasms/pathology
• Neoplasms/therapy
• Tumor Escape
• Tumor Microenvironment

The non-classical HLA-G is a well-known immune-modulatory molecule. In physiological condition, HLA-G surface expression is restricted to the maternal–fetal interface and to immune-privileged adult tissues, whereas soluble forms of HLA-G are detectable in various body fluids. HLA-G can be de novo expressed in pathological conditions including tumors, chronic infections, or after allogeneic transplantation. HLA-G exerts positive effects modulating innate and adaptive immune responses and promoting tolerance, or detrimental effects inducing immune escape mechanisms. HLA-G locus, in contrast to classical HLA class I gene, is highly polymorphic in the non-coding 3′ untranslated region (UTR) and in the 5′ upstream regulatory region (5′ URR). Variability in these regions influences HLA-G expression by modifying mRNA stability or allowing posttranscriptional regulation in the case of 3′ UTR or by sensing the microenvironment and responding to specific stimuli in the case of HLA-G promoter regions (5′ URR). The influence of genetic variations on the expression of HLA-G makes it an attractive biomarker to monitor disease predisposition and progression, or response to therapy. Here, we summarize the current knowledge, efforts, and obstacles to generate a general consensus on the correlation between HLA-G genetic variability, protein expression, and disease predisposition. Moreover, we discuss perspectives for future investigation on HLA-G genotype/expression in association with disease predisposition and progression.

• HLA-G
• HLA-G polymorphisms
• autoimmune diseases
• cancer
• immune regulation
• pregnancy

• Colorectal cancer biomarker
• ELISA
• Non-invasive sampling
• sHLA-G

Overexpression of human leukocyte antigen G (HLA-G) and increased plasma levels of soluble HLA-G (sHLA-G) have been reported in different human malignancies, and are believed to be involved in tumor immune evasion.

This study was designed to evaluate the expression of HLA-G in tumor tissues and the plasma levels of sHLA-G in patients with gastrointestinal cancer, and to determine their associations with clinicopathological factors. The link between Helicobacter pylori infection and increased HLA-G expression or sHLA-G levels was also investigated in patients with gastric cancer.

HLA-G expression was investigated in tumor tissues from 100 patients with gastric and colorectal adenocarcinoma using immunohistochemistry test, and plasma levels of sHLA-G were measured in 82 patients with ELISA method. The presence of H. pylori genome was investigated in tumor tissues from 25 patients with gastric cancer by PCR method.

HLA-G expression was observed in 43% of colorectal cancers and 34.6% of gastric cancers, and was not related with any of the clinicopathological factors. There was a significant correlation between increased sHLA-G level and stage I tumors. Eight of 25 (32%) gastric cancer specimens were positive for H. pylori, of which 3 samples were positive for HLA-G. Soluble HLA-G levels were above the cut-off value in all H. pylori-positive patients.

Plasma levels of sHLA-G were significantly increased in our patients with a sensitivity of 89% and a specificity of 62%. Soluble HLA-G level can be considered a useful indicator for the early diagnosis of gastric and colorectal adenocarcinoma.

• HLA-G
• sHLA-G
• colorectal cancer
• gastric cancer
• Helicobacter pylori

Phenotypic heterogeneity has been observed in most malignancies, which represents a considerable challenge for tumor therapy. In recent decades, the biological function and clinical significance of the human leukocyte antigen (HLA)-G have been intensively explored. It is now widely accepted that HLA-G is a critical marker of immunotolerance in cancer cell immune evasion and is strongly associated with disease progress and prognosis for cancer patients. Moreover, it has recently been emphasized that the signaling pathway linking HLA-G and immunoglobulin-like transcripts (ILTs) is considered an immune checkpoint. In addition, HLA-G itself can generate at least seven distinct isoforms, and intertumor and intratumor heterogeneity of HLA-G expression is common across different tumor types. Furthermore, HLA-G heterogeneity in cancers has been related to disease stage and outcomes, metastatic status and response to different therapies. This review focuses on the heterogeneity of HLA-G expression in malignant lesions, and clinical implications of this heterogeneity that might be relevant to personalized treatments are also discussed.

• HLA-G
• cancer
• heterogeneity
• immune evasion
• therapy target

• 5-aza-2-deoxycytidine
• APM
• Acetylation
• CIITA
• Cancer
• Chemokines
• Cytokines
• Epigenetics
• HDAC inhibitors
• HLA
• Immune escape
• Inflammation
• Methylation
• NK cells
• Nonclassical HLA
• SOCS
• TLR

Differential expression of HLA-G has been observed among cancer types and tumors from individuals with the same type of cancer; however, its clinical significance is rather limited. In this study, expression and predictive relevance of HLA-G expression in 457 primary colorectal cancer (CRC, n_colon = 232, n_rectal = 225) patients was investigated. Data showed 70.7% (323/457) of the CRC were HLA-G expression when the above 5% (HLA-G_Low) was considered as positive, which wasn't associated with patient survival (p = 0.109). However, HLA-G expression above 55% (HLA-G_High) was associated with a worse prognosis of CRC patients (p = 0.042). Furthermore, a shorter survival was found for the female (p = 0.042) and elder (p = 0.037) patients whose HLA-G expression was above HLA-G_Low level. HLA-G expression above HLA-G_High level showed a worse prognosis for female (p = 0.013), elder (p = 0.023), colon cancer (p = 0.016), advanced tumor burden (T₃₊₄, p = 0.018), regional lymph node status (N₁₊₂, p = 0.044), and advanced clinical stage patients (AJCC _III+IV, p = 0.037). In conclusion, our results demonstrated for the first time that combination of differential lesion HLA-G expression notably improved the value of traditional survival prediction for CRC patients.

• HLA-G
• colorectal cancer
• prognosis

• Ascitic soluble human leukocyte antigen-G
• benign ascites
• distinguish
• evaluation
• malignant ascites

Human leukocyte antigen-G (HLA-G) is a non-classical HLA molecule, predominantly expressed in cytotrophoblast cells to protect the fetus during pregnancy. Notably, a high frequency of HLA-G expression has been observed in a wide variety of cancer types in previous studies. Furthermore, HLA-G expression in cancer has been considered to be detrimental, since it can protect cancer cells from natural killer cell cytotoxic T lymphocyte-mediated destruction, promote tumor spreading and shorten the survival time of patients by facilitating tumor immune evasion. In addition, HLA-G polymorphisms have been investigated in numerous types of cancer and are considered as risk factors and predictive markers of cancer. This review focuses on HLA-G expression and its polymorphisms in cancer, analyzing the mechanisms of HLA-G in promoting cancer development, and evaluating the potential and value of its clinical application as a diagnostic and prognostic biomarker, or even as a prospective therapeutic target in certain types of tumors.

• cancer
• genetic polymorphism
• human leukocyte antigen-G
• immune evasion
• therapeutic target
• tumor development

To investigate the association between 16 insertion-deletions (INDEL) polymorphisms, colorectal cancer (CRC) risk and clinical features in an admixed population.

One hundred and forty patients with CRC and 140 cancer-free subjects were examined. Genomic DNA was extracted from peripheral blood samples. Polymorphisms and genomic ancestry distribution were assayed by Multiplex-PCR reaction, separated by capillary electrophoresis on the ABI 3130 Genetic Analyzer instrument and analyzed on GeneMapper ID v3.2. Clinicopathological data were obtained by consulting the patients’ clinical charts, intra-operative documentation, and pathology scoring.

Logistic regression analysis showed that polymorphism variations in IL4 gene was associated with increased CRC risk, while TYMS and UCP2 genes were associated with decreased risk. Reference to anatomical localization of tumor Del allele of NFKB1 and CASP8 were associated with more colon related incidents than rectosigmoid. In relation to the INDEL association with tumor node metastasis (TNM) stage risk, the Ins alleles of ACE, HLAG and TP53 (6 bp INDEL) were associated with higher TNM stage. Furthermore, regarding INDEL association with relapse risk, the Ins alleles of ACE, HLAG, and UGT1A1 were associated with early relapse risk, as well as the Del allele of TYMS. Regarding INDEL association with death risk before 10 years, the Ins allele of SGSM3 and UGT1A1 were associated with death risk.

The INDEL variations in ACE, UCP2, TYMS, IL4, NFKB1, CASP8, TP53, HLAG, UGT1A1, and SGSM3 were associated with CRC risk and clinical features in an admixed population. These data suggest that this cancer panel might be useful as a complementary tool for better clinical management, and more studies need to be conducted to confirm these findings.

• Colorectal cancer
• Ins-del polymorphism
• Admixed population
• Potential biomarker
• Diagnostic
• Risk stratification
• Prognostic
• Clinical features

• Adult
• Aged
• Aged, 80 and over
• Brazil/epidemiology
• Case-Control Studies
• Colorectal Neoplasms/epidemiology
• Colorectal Neoplasms/genetics
• Electrophoresis, Capillary
• Female
• Genetic Predisposition to Disease
• Genotype
• Genotyping Techniques/instrumentation
• Genotyping Techniques/methods
• Humans
• INDEL Mutation/genetics
• Incidence
• Male
• Middle Aged
• Polymorphism, Genetic/genetics
• Risk Factors

• HLA-G
• chronic hepatitis B
• deletion polymorphism

Qa-2 is believed to mediate a protective immune response against cancer; however, little is known about the role of Qa-2 in tumorigenesis. Here, we used 4T1 breast cancer cells to study the involvement of Qa-2 in tumor progression in a syngeneic host. Qa-2 expression was reduced during in vivo tumor growth and in cell lines derived from 4T1-induced tumors. Tumor-derived cells elicited an epithelial-mesenchymal transition associated with upregulation of Zeb1 and Twist1/2 and enhanced tumor initiating and invasive capacities. Furthermore, these cells showed increased stem characteristics, as demonstrated by upregulation of Hes1, Sox2 and Oct3/4, and enrichment of CD44^high/CD24^median/low cells. Remarkably, Qa-2 cell-surface expression was excluded from the CD44^high/CD24^median/low subpopulation. Tumor-derived cells showed increased Src activity, and treatment of these cells with the Src kinase inhibitor PP2 enhanced Qa-2 but reduced Sox2 and CD44^high/CD24^median/low expression levels, suggesting that Src signaling, while positively associated with stemness, negatively regulates Qa-2 expression in breast cancer. Finally, overexpression of the Qa-2 family member Q7 on the cell surface slowed down in vivo tumor growth and reduced the metastatic potential of 4T1 cells. These results suggest an anti-malignant role for Qa-2 in breast cancer development, which appears to be absent from cancer stem cells.

• checkpoint inhibition
• colorectal cancer
• immunotherapy

Polymorphisms in drug-metabolizing enzymes might not completely explain inter-individual differences in toxicity profiles of patients with colorectal cancer (CRC) that receive folinic acid/5-fluorouracil/oxaliplatin (FOLFOX4). Recent data indicate that the immune system could contribute to FOLFOX4 outcomes. In light of the immune inhibitory nature of human leukocyte antigen-G (HLA-G), a non-classical major histocompatibility complex (MHC) class I molecule, we aimed to identify novel genomic markers of grades 3 and 4 (G3-4) toxicity related to FOLFOX4 therapy in patients with CRC. We retrospectively analyzed data for 144 patients with stages II-III CRC to identify HLA-G 3′ untranslated region (3′UTR) polymorphisms and related haplotypes and evaluate their impact on the risk of developing G3-4 toxicities (i.e., neutropenia, hematological/non-hematological toxicity, neurotoxicity) with logistic regression. The rs1610696-G/G polymorphism was associated with increased risk of G3-4 neutropenia (OR = 3.76, p = 0.015) and neurotoxicity (OR = 8.78, p = 0.016); rs371194629-Ins/Ins was associated with increased risk of neurotoxicity (OR = 5.49, p = 0.027). HLA-G 3′UTR-2, which contains rs1610696-G/G and rs371194629-Ins/Ins polymorphisms, was associated with increased risk of G3-4 neutropenia (OR = 3.92, p = 0.017) and neurotoxicity (OR = 11.29, p = 0.009). A bootstrap analysis confirmed the predictive value of rs1610696 and rs371194629, but the UTR-2 haplotype was validated only for neurotoxicity. This exploratory study identified new HLA-G 3′UTR polymorphisms/haplotypes as potential predictive markers of G3-4 toxicities in CRC.

• colorectal cancer
• folinic acid/5-fluorouracil/oxaliplatin
• human leukocyte antigen-G 3′UTR
• immunogenetics
• polymorphism
• toxicity

Although immune system plays a key role in the pathogenesis of both endometriosis and ovarian cancer, its function is different. Therefore, we hypothesized, that selected immune parameters can serve as diagnostic markers of these two conditions. The aim of this study was to compare serum and peritoneal fluid concentrations of sHLA-G, IL-10 and TNF-alpha in women with selected ovarian pathologies: benign serous cysts, endometrioma and malignant tumors. Clinical significance of using them for diagnostic purposes in women with serous ovarian cysts, endometriosis, and ovarian cancer, which in the future may improve the early diagnosis of ovarian diseases.

The study included women treated surgically for benign serous ovarian cysts, ovarian endometrioma and serous ovarian adenocarcinomas. Peripheral blood and peritoneal fluid samples were obtained intraoperatively.

Patients with benign serous cysts, endometrioma and ovarian malignancies did not differ significantly in terms of their serum and peritoneal fluid concentrations of sHLA-G. Ovarian cancer patients presented with significantly higher median serum concentrations of IL-10 and TNF-alpha than other study subjects. Median concentrations of IL-10 and TNF-alpha in peritoneal fluid turned out to be the highest in ovarian cancer patients, followed by women with endometrioma and subjects with benign serous cysts. All these intergroup differences were statistically significant. Irrespective of the group, median concentrations of sHLA-G, IL-10 and TNF-alpha in peritoneal fluid were higher than serum levels of these markers.

Elevated serum and peritoneal fluid concentrations of IL-10 and TNF-alpha distinguish ovarian malignancies and endometriomas from benign serous ovarian cysts. In contrast to endometriosis, ovarian malignancies are characterized by elevated peritoneal fluid concentrations of IL-10 and TNF-alpha, elevated serum concentrations of IL-10 and low serum levels of TNF-alpha. Serum and peritoneal fluid concentrations of sHLA-G have no diagnostic value in differentiating between ovarian malignancies and endometriomas.

• Endometriosis
• IL-10
• Ovarian cancer
• Ovarian cysts
• TNF-alpha
• Tumor escape
• sHLA-G

• HLA-G
• colorectal cancer
• liver metastasis
• mucinous carcinoma
• prognostic biomarker
• tumour immune evasion
• vascular invasion

• Cancer treatment
• HLA
• KIR
• NK cells
• T cells
• Tumor immune evasion

• HLA Antigens/genetics
• HLA Antigens/metabolism
• Humans
• Neoplasms/therapy
• Receptors, KIR/genetics
• Receptors, KIR/metabolism
• Treatment Outcome

• CRC
• cancer immunoediting
• clinical trials
• colorectal cancer
• immune system
• immunotherapy
• tumor microenvironment

• Antígeno leucocitario humano-G
• Bronchoalveolar Lavage
• Cáncer de pulmón
• Human Leukocyte Antigen-G
• Karnofsky index
• Lavado broncoalveolar
• Lung cancer
• Índice de Karnofsky

• 3' Untranslated Regions
• Colorectal Neoplasms/drug therapy
• Colorectal Neoplasms/genetics
• Colorectal Neoplasms/immunology
• Disease-Free Survival
• Female
• Genotype
• HLA-G Antigens/genetics
• Humans
• Male
• Middle Aged
• Polymorphism, Single Nucleotide
• Prognosis