Figure 6.

(A-C) Tumors of patients resistant to checkpoint inhibitor treatment are not enriched for HLA-A or B2M loss despite association of B2M expression with CD8 infiltration and PDL1 expression. (A) Increased frequency of CD8+ inflamed immune phenotype in tumors with B2M expression. The respective proportion of metastatic tumors with CD8+ inflamed, excluded or desert phenotype is compared between tumors displaying loss or positive HLA-A or B2M expression status. Tumors positive for B2M show a relative increase in proportion of CD8+ T-cell inflamed tumors (p< 0.05, χ²-test for equal proportions). (B) B2M positivity is associated with PDL1 expression. Distribution of tumor PDL1 expression in specimens which are either positive or negative for HLA-A and B2M, assessed at the time of enrolment in a Roche-sponsored clinical trial. Tumors positive for B2M were more likely to express PDL1 than those that were B2M negative and the difference was statistically significant (n = 155, p-value< 0.001, logistic regression adjusted for two clinical PDL1 staining procedures, see methods for details). (C) Tumors of patients resistant to prior checkpoint inhibitor treatment are not enriched for HLA-A or B2M loss. The figure illustrates distribution of HLA-A and B2M expression in tumors from patients who were CPI-experienced or CPI- naive at the time of the biopsy. CPI-experienced patients had advanced disease and had failed at least one prior line of checkpoint inhibitor treatment. They were therefore eligible for and enrolled in an early-phase 1 clinical trial, testing a new investigative treatment as monotherapy or as a combination. CPI-naive patients were patients with advanced disease who were enrolled in an early-phase clinical trial and consequently were not on standard-of-care treatment or had failed at least one prior line of non-CPI therapy. Difference in proportions was tested with a χ²-test and sample numbers are given for each group.