Background: Prior studies with crefmirlimab, a 89-Zr labeled antibody with specificity for CD8+ cells, have shown a strong correlation with SUV uptake and IHC of the same lesions validating its use (Pal 2023). We predicted that responders to IO therapy would have higher CD8 lymph node avidity than non-responders. Methods: Pts enrolled had a diagnosis of mRCC and must have received IO therapy (CPI/TKI, CPI/CPI, or CPI monotherapy). Pts obtained a crefmirlimab PET/CT within 1 week before CPI infusion as baseline. PET intensity was determined using SUV_Max, SUV_Mean, SUV_Peak. Highly avid lymph nodes (SUV_Max> 10) were quantified. Best overall response was determined using RECIST 1.1 criteria with SUV values and number of CD8 PET-avid lymph nodes compared using a Wilcoxon Signed Rank test in R. Results: A total of 17 pts (9 M: 8 F) were enrolled across 3 sites with 9 pts locally available for analysis. The median age of pts was 64 years old (54-71). Histology types included 12 clear cell (71%), 2 papillary (12%), and 3 indeterminate (17%). There were 3 responders (18%), 12 non-responders (71%), and 2 non-evaluable (12%). The most common treatment regimens patients received in descending order were cabozantinib + nivolumab (44.44%), nivolumab (33.33%), and ipilimumab + nivolumab (22.22%). Strong correlation was observed between CD8 cell density and SUV_Mean (p <0.0003 by Spearman’s correlation). The average number of CD8 PET-avid lymph nodes (defined as SUV_Max> 10) in responders was 6 versus 1.17 in non-responders (p = 0.025, 95% CI [1.99,7]). SUV_Max, SUV_Mean, SUV_Peak across all CD8 PET-avid lymph nodes for responders were 15.58, 12.63, 11.44 and for non-responders were 9.86, 8.53, 7.79 respectively. The difference between SUV_Max, SUV_Mean, SUV_Peak values reached statistical significance for all three values (p = 0.023 95% CI [3.42,7.84], p = 0.023 95% CI [2.64,5.84], p = 0.029 95% CI [1.18, 5.41] respectively). Conclusions: Our results show that pts with higher number of CD8 PET-avid lymph nodes at baseline was associated with better response to IO therapy; responders also had overall higher SUV uptake in CD8 PET-avid lymph nodes than non-responders. Our findings suggest that those with a more enriched CD8 phenotype trended towards better outcomes and may be a reliable predictor for IO therapy response. Clinical trial information: NCT03802123.