Understanding factors that shape the immune landscape across hematological malignancies is essential for immunotherapy development. We integrated over 8,000 transcriptomes and 2,000 samples with multilevel genomics of hematological cancers to investigate how immunological features are linked to cancer subtypes, genetic and epigenetic alterations, and patient survival, and validated key findings experimentally. Infiltration of cytotoxic lymphocytes was associated with TP53 and myelodysplasia-related changes in acute myeloid leukemia, and activated B cell-like phenotype and interferon-γ response in lymphoma. CIITA methylation regulating antigen presentation, cancer type-specific immune checkpoints, such as VISTA in myeloid malignancies, and variation in cancer antigen expression further contributed to immune heterogeneity and predicted survival. Our study provides a resource linking immunology with cancer subtypes and genomics in hematological malignancies.

了解影响血液恶性肿瘤免疫格局的因素对于免疫疗法的发展至关重要。我们将8,000多个转录组和2,000个样本与血液癌症的多基因组学整合在一起，以研究免疫学特征如何与癌症亚型，遗传和表观遗传学改变以及患者生存率相关联，并通过实验验证了主要发现。细胞毒性淋巴细胞的浸润与TP53和急性髓性白血病中与骨髓增生相关的变化有关，并与淋巴瘤中活化的B细胞样表型和干扰素-γ反应有关。CIITA甲基化调节抗原呈递，癌症类型特异性免疫检查点（如髓样恶性肿瘤中的VISTA）以及癌症抗原表达的变化进一步有助于免疫异质性和预测的存活率。我们的研究提供了将免疫学与血液恶性肿瘤中的癌症亚型和基因组学联系起来的资源。