Tumor MHC Expression Guides First-Line Immunotherapy Selection in Melanoma.

Area of Science:

• Oncology
• Immunology
• Dermatology

Background:

• Immunotherapy targeting PD-1 and CTLA-4 has improved outcomes for advanced melanoma.
• Combination immunotherapy offers higher response rates than monotherapy but increases toxicity.
• Lack of predictive biomarkers hinders optimal first-line immunotherapy selection.

Purpose of the Study:

• To investigate the role of MHC class I (MHC-I) expression as a biomarker for predicting response to melanoma immunotherapy.
• To correlate MHC-I expression levels with treatment outcomes in patients receiving anti-PD-1 or combination immunotherapy.

Main Methods:

• Flow cytometry was used to analyze pretreatment tumor biopsies from 36 melanoma patients.
• A quantitative score was developed to assess tumor cell expression of MHC class I molecules.
• MHC-I expression data were correlated with treatment response to anti-PD-1 or combination immunotherapy.

Main Results:

• Intact MHC-I expression was observed in all tumors from patients with durable response to anti-PD-1 monotherapy.
• Low MHC-I expression was found in 67% of tumors from patients with durable response to combination immunotherapy.
• MHC-I low tumors showed reduced T-cell infiltration and a myeloid-rich microenvironment.

Conclusions:

• Robust MHC-I expression is crucial for response to anti-PD-1 monotherapy in melanoma.
• Low MHC-I expression suggests a rationale for using combination immunotherapy as a first-line treatment in melanoma.