Proliferative exhausted CD8+ T cells exacerbate long-lasting anti-tumor effects in human papillomavirus-positive head and neck squamous cell carcinoma

Abstract

The survival prognosis of human papillomavirus (HPV)-positive and HPV-negative head and neck squamous cell carcinoma (HNSCC) is largely different, and little is known about the anti-tumor mechanism of tumor-infiltrated exhausted CD8+ T cells (Tex) in HNSCC. We performed cell-level multi-omics sequencing on human HNSCC samples to decipher the multi-dimensional characteristics of Tex cells. A proliferative exhausted CD8+ T cell cluster (P-Tex) which was beneficial to survival outcomes of patients with HPV-positive HNSCC was identified. Interestingly, P-Tex cells expressed CDK4 genes as high as cancer cells, which could be simultaneously inhibited by CDK4 inhibitors and might be a potential reason for the ineffectiveness of CDK4 inhibitors in treating HPV-positive HNSCC. P-Tex cells could aggregate in the antigen-presenting cell niches and activate certain signaling pathways. Together, our findings suggest a promising role for P-Tex cells in the prognosis of patients with HPV-positive HNSCC by providing modest but persistent anti-tumor effects.

High-resolution transcriptomics analysis of CXCL13+ EPSTI1+ CDK1+ cells with a specific focus on lung adenocarcinoma

“…Previous studies have shown that CDK1 and CDK inhibitors could regulate the IFN pathway ( 46 , 47 ). Emerging evidence also suggests that CDK4 , another member of the CDK family may affect T-cell survival ( 48 ). In this study, we have identified relevant targets of CDK1 , such as GALNT2 and VCAM1 .…”

The Eradication of Carcinogenic Viruses in Established Solid Cancers

“… 25 In female mice, intravaginal immunization with HPV followed by boosting with different HPV serotypes resulted in a 10-fold increase in cervicovaginal antigen-specific CD8+ T cells compared to priming alone. 12 While “exhausted” CD1+ HPV-specific CD8+ T cell clusters have been observed in the context of HPV-positive head and neck squamous cell carcinoma (HNSCC), 26 , 27 this cluster contributes to persistent anti-tumor immunity due to their extended cell survival and specialized cytotoxic capacity. 26 Moreover, it has been associated with longer survival in HPV-positive HNSCC.…”

“… 12 While “exhausted” CD1+ HPV-specific CD8+ T cell clusters have been observed in the context of HPV-positive head and neck squamous cell carcinoma (HNSCC), 26 , 27 this cluster contributes to persistent anti-tumor immunity due to their extended cell survival and specialized cytotoxic capacity. 26 Moreover, it has been associated with longer survival in HPV-positive HNSCC. 26 Notably, no reports exist of exhausted anti-HPV CD8+ T cells in the context of HPV infection in non-cancerous tissue.…”

“… 26 Moreover, it has been associated with longer survival in HPV-positive HNSCC. 26 Notably, no reports exist of exhausted anti-HPV CD8+ T cells in the context of HPV infection in non-cancerous tissue.…”

The diversity of inhibitory receptor co-expression patterns of exhausted CD8+ T cells in oropharyngeal carcinoma

“…Some researchers consider IR co-expression as an indication of T cell exhaustion, whereas others claim it defines a subset of activated and functional effector cells. 12 , 13 , 14 For example, early exhausted PD-1 + T cells (Tex) cells can be reinvigorated by anti-programmed cell death-ligand 1 (PD-L1) treatment, whereas terminally exhausted Tex cells expressing PD-1, LAG3, or TIM3 are unresponsive to anti-PD-1 or PD-L1 treatment. 15 The impact on anti-tumor response and potential change of co-expression pattern of IRs after immune checkpoint inhibitor (ICI) treatment remains unclear.…”