The Concordant Disruption of B7/CD28 Immune Regulators Predicts the Prognosis of Oral Carcinomas

• Published in: International journal of molecular sciences Vol. 24; no. 6; p. 5931
• Main Authors: Chang, Shi-Rou, Chou, Chung-Hsien, Liu, Chung-Ji, Lin, Yu-Cheng, Tu, Hsi-Feng, Chang, Kuo-Wei, Lin, Shu-Chun
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.03.2023; MDPI
• Subjects: Antigens; B7 Antigens - genetics; B7-1 Antigen - metabolism; B7-H1 Antigen - genetics; B7-H1 Antigen - metabolism; Carcinoma, Squamous Cell - pathology; CD28; CD28 antigen; CD28 Antigens; CD8 antigen; CD8-Positive T-Lymphocytes - metabolism; CD80 antigen; CD86 antigen; Cell Adhesion Molecules; CTLA-4 protein; Dendritic cells; Disruption; Head & neck cancer; head and neck cancer; Head and Neck Neoplasms; Humans; immune modulator; Immune system; Immunologic Factors; Immunological memory; Immunomodulation; Immunotherapy; Ligands; lymph node; Lymphocytes; Lymphocytes B; Lymphocytes T; Macrophages; Malignancy; Medical prognosis; Memory cells; metastasis; Mouth Neoplasms - pathology; Oral cancer; Oral carcinoma; Oral squamous cell carcinoma; Papillomavirus infections; Pathogenesis; Patients; PD-L1 protein; Prognosis; Ratios; Squamous cell carcinoma; Squamous Cell Carcinoma of Head and Neck; Survival; Transcriptomes; Tumor Microenvironment; Tumors; Taiwan; head and neck cancer; B7; metastasis; lymph node; CD28; immune modulator; oral cancer
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms24065931

Immune modulation is a critical factor in determining the survival of patients with malignancies, including those with oral squamous cell carcinoma (OSCC) and head and neck SCC (HNSCC). Immune escape or stimulation may be driven by the B7/CD28 family and other checkpoint molecules, forming ligand-receptor complexes with immune cells in the tumor microenvironment. Since the members of B7/CD28 can functionally compensate for or counteract each other, the concomitant disruption of multiple members of B7/CD28 in OSCC or HNSCC pathogenesis remains elusive. Transcriptome analysis was performed on 54 OSCC tumors and 28 paired normal oral tissue samples. Upregulation of CD80, CD86, PD-L1, PD-L2, CD276, VTCN1, and CTLA4 and downregulation of L-ICOS in OSCC relative to the control were noted. Concordance in the expression of CD80, CD86, PD-L1, PD-L2, and L-ICOS with CD28 members was observed across tumors. Lower ICOS expression indicated a worse prognosis in late-stage tumors. Moreover, tumors harboring higher PD-L1/ICOS, PD-L2/ICOS, or CD276/ICOS expression ratios had a worse prognosis. The survival of node-positive patients was further worsened in tumors exhibiting higher ratios between PD-L1, PD-L2, or CD276 and ICOS. Alterations in T cell, macrophage, myeloid dendritic cell, and mast cell populations in tumors relative to controls were found. Decreased memory B cells, CD8 T cells, and Tregs, together with increased resting NK cells and M0 macrophages, occurred in tumors with a worse prognosis. This study confirmed frequent upregulation and eminent co-disruption of B7/CD28 members in OSCC tumors. The ratio between PD-L2 and ICOS is a promising survival predictor in node-positive HNSCC patients.