KEY TAKEAWAYS
- The MEDI4736 phase 2 trial targeted to identify cellular and molecular markers for immunotherapy in pts with HPV+ OPSCC.
- Targeting CD161 in Trm may boost immunotherapy in pts with HPV+ OPSCC.
Oropharyngeal squamous cell carcinoma (OPSCC) in patients (pts) with positive human papillomavirus (HPV+) is positively associated with more favorable clinical outcomes relative to HPV- OPSCC. However, the effectiveness of immunotherapy in pts with HPV+ OPSCC remains uncertain.
Junha Cha and the team aimed to identify cellular and molecular factors inhibiting the benefits of HPV in OPSCC immunotherapy through single-cell RNA (scRNA) and T-cell receptor sequencing analyses of tumor biopsies which were validated by using immunofluorescence and publicly available transcriptomics data sets.
Researchers noted significantly higher transcriptional diversity in malignant cells, evident among non-responders to immunotherapy, irrespective of HPV infection status. A notably high proportion of CD4+ follicular helper T cells (Tfh) was observed indicating an enhanced Tfh differentiation in HPV+ tumors.
They noted an elevated KLRB1 (expression in CD8+ resident memory T cells (Trm) in HPV+ OPSCC was linked to decreased antitumor activity, possibly impacting clinical outcomes. Additionally, the correlation between elevated KLRB1 levels in Trm and low CLEC2D expression in B cells among HPV+ pts may reduce tertiary lymphoid structure-activity, while immunofluorescence analysis of HPV+ tumors treated with immune checkpoint blockade demonstrated an inverse correlation between CD161+ Trm density and tumor size changes.
The study concluded that targeting CD161 in Trm cells could potentially improve the efficacy of immunotherapy in HPV+ OPSCC by mitigating the counteractive effects on clinical benefits associated with HPV.
The trial was sponsored by Yonsei University.
Source: https://pubmed.ncbi.nlm.nih.gov/38857913/
Clinical Trial: https://clinicaltrials.gov/study/NCT03737968
Cha J., Kim D.H., Kim G., et al. (2024). “Single-cell analysis reveals cellular and molecular factors counteracting HPV-positive oropharyngeal cancer immunotherapy outcomes.” J Immunother Cancer. 2024 Jun 10;12(6):e008667. doi: 10.1136/jitc-2023-008667. PMID: 38857913.
