Serum sHLA-G: Significant diagnostic biomarker with respect to therapy and immunosuppressive mediators in Head and Neck Squamous Cell Carcinoma

Abstract

Demographic characteristics of study groups. The baseline data of both study groups have been provided in Table 1. We noticed higher frequency of male subjects in both groups in comparison to female subjects. Patients having tobacco consumption habit (62.5%) were more prevalent in the study cohort. Patients with oral cavity site, node involvement, later stages of tumor and MDSCC histopath were more. Estimation of HLA-G, IL-10 and IFN-γ protein level in the study population. By SPR. The standard curves obtained by plotting different concentration of purified proteins and respective RU values are in linear range (Fig. S1). One RU corresponds to immobilized protein concentration of 1 pg/mm2. The RU shows linear relation with concentration of protein which signifies sensitivity of the protein. The protein concentration of all serum samples were estimated using standard curve equation. The concentration of sHLA-G (8.25 ± 1.74 ng/µl), IL-10 (43.99 ± 11.13 ng/µl) and IFN-γ (20.04 ± 9.70 ng/µl) protein levels were higher in serum of HNSCC patients in comparison to controls (sHLA-G: 6.45 ± 1.31; IL-10:37.08 ± 8.55; IFN-γ:16.19 ± 6.60 ng/µl). The obtained range of protein concentration of serum sHLA-G, serum IL-10, and serum IFN-γ in HNSCC patients were 6.04-18 ng/µl, 22.59-75.04 ng/µl and 9.02-59.13 ng/µl, respectively. sHLA-G protein concentration was elevated (8.09 ± 1.79 ng/µl) in patient group which was observed to be declined in concentration levels after therapy (6.64 ± 1.33 ng/µl) which showed response to the therapy on the basis of this protein (Fig. 1). In case of IL-10, the protein concentration was reported 42.43 ± 11.30 ng/µl before therapy and dropped to 34.66 ± 8.33 ng/µl and IFN-γ protein concentration was found 17.45 ± 7.80 ng/µl at the time of diagnosis which declines to 13.62 ± 5.22 ng/µl after completion of therapy (Fig. 1a-c). Receiver-operating characteristic (ROC) curves were prepared to determine diagnostic performance of sHLA-G for HNSCC, where area under curve (AUC) and the cutoff value were 0.81 and ≥7.08 ng/µl with the sensitivity and specificity of 74.67 and 74.17, respectively (Fig. 2).

The Potential of Soluble Human Leukocyte Antigen Molecules for Early Cancer Detection and Therapeutic Vaccine Design

“…To complete the overview of sHLA-G in cancer, in Table 2 all studies were included that were either performed after 2017 or that were missing in the referenced papers. In summary, most recent studies assessing sHLA-G in the context of solid tumors found increased levels in patient samples [ 5 , 6 , 7 , 32 , 33 , 34 ] ( Table 2 , upper part). A few studies also included non-malignant diseases as their control cohorts [ 35 , 36 , 37 , 38 , 39 ].…”

“…In a few studies, sHLA-G levels also positively correlated with more advanced disease stage [ 5 , 6 , 7 , 33 , 38 , 45 , 46 ]. In CRC, however, sHLA-G levels were found to have contrasting prognostic values depending on the TNM stage [ 43 ], illustrating that using HLA-G as a solid tumor biomarker may not always be straightforward.…”

“…Extending upon this, the number of studies that perform a receiver operating characteristic (ROC) analysis (plotting the relation between sensitivity and specificity) to assess the discriminative power of sHLA as a biomarker is limited. Although only partially informative due to the lack of proper non-malignant control groups, the described area under the curve (AUC) for sHLA-G to discriminate cancer patients from healthy controls was significantly different from chance (AUC = 0.5) in all reporting studies and ranged from 0.6 to 0.842 [ 33 , 35 , 36 , 39 , 44 , 50 ]. From these studies, three report on a good discriminative power of sHLA-G between malignancy and other, non-malignant diseases, although two of those mixed non-malignant control samples with healthy controls for ROC analysis [ 35 , 36 , 39 ].…”

HLA-G/sHLA-G and HLA-G-Bearing Extracellular Vesicles in Cancers: Potential Role as Biomarkers

“…In terms of diagnosis, sHLA-G is abnormally expressed in the plasma in breast ductal carcinoma ( 131 ), head and neck squamous cell carcinoma ( 129 ), gastric cancer ( 33 ), CRC ( 125 ), and papillary thyroid carcinoma ( 65 ), which is considered to be a preoperative diagnosis of cancer histopathology potential marker of aggressiveness. It is worth noting that in gastric cancer, researchers have found that sHLA-G in combination with common serum tumor markers, such as CA72-4, CA125, and CA19-1, can improve the clinical screening of gastric cancer compared with sHLA-G alone ( 132 ).…”

Single-Domain Antibody-Based TCR-Like CAR-T: A Potential Cancer Therapy

“…The secreted cytokines include interleukin 10 (IL-10), which might promote T regulatory cell (Treg) suppressive activity or increase the expression of the immunosuppressive molecule like HLA-G. Meanwhile, the transforming growth factor beta (TGF- β ), which has a well-known immunosuppressive role, garners much attention in this field [ 36 – 40 ].…”