Methods to predict the efficacy of neoadjuvant anti-pd-1 therapy in resectable oral-cavity squamous cell carcinoma and target post-surgical relapses

A method of treating a subject in need of treatment for resectable head and neck cancer, the method comprising:

• (a) assaying a biological sample obtained from the subject for at least one of:
• (1) tumor mutational burden (TMB) in tumor cells,
• (2) mutations in FLT4, PTEN, YAP1, and/or JAK2 in tumor cells,
• (3) signature enrichment or mutational status in PTEN in tumor cells,
• (4) ratio of regulatory T to TH17 cells in peripheral blood mononuclear cells (PBMCs),
• (5) scoring of tumor-infiltrating cytolytic T cells;
• (6) T cell receptor (TCR) diversity and clonality in tumors or in PBMCs at a first time point and at a second time point;
• and
• (b) treating the subject with:
• (1) neoadjuvant anti-PD-1/L1 therapy prior to surgical resection when the assaying of (a) detects:
• (i) greater than 5.8 mutations per megabase (Mb) in tumor cells,
• (ii) mutations in FLT4 in tumor cells,
• (iii) signature enrichment of PTEN or wildtype PTEN,
• (iv) a ratio of regulatory T cells to TH17 cells of ≤4 in PBMCs;
• and/or
• (v) brisk tumor infiltration of cytolytic T cells;
• and
• (2) surgical resection without neoadjuvant anti-PD-1 therapy when the assaying of (a) detects:
• (i) less than 5.8 mutations per megabase (Mb) in tumor cells,
• (ii) mutations in PTEN, YAP1, and/or JAK2 in tumor cells,
• (iii) a ratio of regulatory T cells to TH17 cells of greater than 4 in PBMCs;
• (iv) a reduction in TCR diversity or increase in TCR clonality in PBMCs at the second time point compared to the first time point;
• and/or
• (v) non-brisk tumor infiltration of cytolytic T cells.