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Related Experiment Video

Updated: Sep 28, 2025

Testing Cancer Immunotherapeutics in a Humanized Mouse Model Bearing Human Tumors

Testing Cancer Immunotherapeutics in a Humanized Mouse Model Bearing Human Tumors

Published on: December 16, 2022

HLA class II immunogenic mutation burden predicts response to immune checkpoint blockade.

X M Shao¹, J Huang², N Niknafs³

¹Institute for Computational Medicine, Johns Hopkins University, Baltimore, USA; Department of Biomedical Engineering, Johns Hopkins University, Baltimore, USA.

Annals of Oncology : Official Journal of the European Society for Medical Oncology

|March 27, 2022

Summary

Higher human leukocyte antigen (HLA) class II immunogenic mutation (IMM) burden predicts better response to immune checkpoint blockade (ICB) in melanoma and lung cancer patients. This suggests HLA class II IMMs play a distinct, complementary role in tumor rejection and patient survival.

Keywords:

HLA class II neoantigens clinical outcome immune checkpoint blockade immunogenic mutations

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Predictive Immune Modeling of Solid Tumors

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Published on: February 25, 2020

Area of Science:

Immunology
Oncology
Genomics

Background:

Human leukocyte antigen (HLA) class I neoantigens are linked to immune checkpoint blockade (ICB) response.
The role of HLA class II-restricted neoantigens in ICB response remains less understood.

Purpose of the Study:

To computationally assess HLA class II immunogenic mutation (IMM) burden in patients with melanoma and lung cancer treated with ICB.
To evaluate the impact of HLA class II IMMs on clinical outcomes and tumor microenvironment.

Main Methods:

Analysis of whole-exome sequence data from ICB-treated melanoma and non-small-cell lung cancer (NSCLC) cohorts.
Utilized MHCnuggets to estimate HLA class II IMM burdens and mutation clonality.
Correlated HLA class II IMM burden with clinical outcomes, T-cell infiltration, and gene expression.

Main Results:

Responding tumors showed significantly higher HLA class II IMM burden in both melanoma and NSCLC.
Higher HLA class II IMM burden correlated with longer survival, especially in NSCLC with low heterogeneity.
Distinct HLA class I and II IMM landscapes suggest complementary roles in tumor rejection.
Increased HLA class II IMM burden associated with CD4+ T-cell infiltration and an inflamed tumor microenvironment.

Conclusions:

HLA class II IMM burden is a significant predictor of longer survival in patients receiving ICB.
HLA class II IMMs may influence ICB response distinctly and complementarily to HLA class I.