TP53 A159V

We also validated this finding by immunofluorescent staining of PD-L1 and M2 Macrophages in immunocompetent mouse HNSCC xenografts models expressing RAC1 p.P29S and p.A159V mutations as compared to controls.Our in silico, in vitro and in vivo findings first uncover an important role of RAC1 aberrations in HNSCC TIME immunosuppression by regulating PD-L1 expression, neutrophil and M2 macrophages infiltrations. Clinical activities of PD-L1 inhibitors in RAC1-mutated HNSCC patients worth future investigations.

This study is the largest on the cytomorphologic and immunohistochemical characteristics of isolated TP53 -mutated LUAC. Recognizing this diverse molecular subset is important in predicting poor clinical outcomes.

On the other hand, in Rac1-GTP, some of the contacts of the guanosine ring of GTP with Rac1 are temporarily lost, enabling the guanosine ring to move toward Switch I and subsequently close the switch. Rac1-GTP adopts a Ras state 2 like conformation, where both switch regions are in closed conformation and Thr35 forms a hydrogen bond with the nucleotide.

RAC1 amplification and gain, which accounts for 39.5% of HNSCC are also significantly associated with poorer OS and DFS (P<0.01).While HNSCC is one of the most highly immune infiltrated cancer types with promising results in clinical trials of immune checkpoint inhibitors, e.g. nivolumab, we examined the potential involvement of immune-related events to the dismal outcomes of RAC1-mutated HNSCC patients...We also examined the mRNA expression of the immunomodulatory genes in RAC1-mutated vs. RAC1-wildtype HNSCC tumors. RAC1-mutated patients have significantly higher expression of pro-inflammatory CXCL9 and CXCL10 (p=0.01) as well as druggable targets CD274 (PD-L1) (p=0.014) and IL2 (p<0.01).Taken together, RAC1 mutations may contribute to an immunosuppressive tumor microenvironment in HNSCC, first highlighting potential immunological roles of RAC1 aberrations in HNSCC.