肺癌中KRAS/STK11共突变亚型的两面性：免疫学悖论与治疗机遇

doi:10.3760/cma.j.cn371439-20251128-00099

国际肿瘤学杂志 ›› 2026, Vol. 53 ›› Issue (10): 628-634.doi: 10.3760/cma.j.cn371439-20251128-00099

肺癌中KRAS/STK11共突变亚型的两面性：免疫学悖论与治疗机遇

高密¹, 干葵², 朱军³, 黄美金³()

¹ 联勤保障部队第九二〇医院中医科，昆明 650032
² 联勤保障部队第九二〇医院骨科，昆明 650032
³ 联勤保障部队第九二〇医院肿瘤科，昆明 650032

收稿日期:2025-11-28 出版日期:2026-10-08 发布日期:2026-10-10
通讯作者: 黄美金，Email：hmj986@163.com
作者简介:高密和干葵对本文有同等贡献
基金资助:
云南省应用基础研究项目(202401AY070001-275)

Duality of KRAS/STK11 co-mutation subtype in lung cancer：immunological paradox and therapeutic opportunities

Gao Mi¹, Gan Kui², Zhu Jun³, Huang Meijin³()

¹ Department of Traditional Chinese Medicine， 920th Hospital of Joint Logistics Support Force， Kunming 650032， China
² Department of Orthopedics， 920th Hospital of Joint Logistics Support Force， Kunming 650032， China
³ Department of Oncology， 920th Hospital of Joint Logistics Support Force， Kunming 650032， China

Received:2025-11-28 Online:2026-10-08 Published:2026-10-10
Contact: Huang Meijin，Email：hmj986@163.com
About author:Gao Mi and Gan Kui are contributed equally to the article
Supported by:
Applied Basic Research Project of Yunnan Province of China(202401AY070001-275)

摘要/Abstract

摘要：

KRAS与STK11（又称LKB1）的共突变为肺癌中一个独特的分子亚型（KL亚型），其特征表现为高肿瘤突变负荷与免疫检查点抑制剂耐药并存的“免疫学悖论”。该亚型的耐药性主要源于多重机制共同塑造的免疫抑制微环境，包括髓系细胞异常募集、代谢重编程及KEAP1/NRF2通路的协同作用。目前，KL亚型的治疗策略已转向多途径联合干预，例如直接靶向KRAS^G12C、调控免疫微环境以及新兴疗法等。尽管临床转化仍面临模型局限、肿瘤异质性和联合毒性等挑战，但通过整合多组学分析、创新试验设计与新兴治疗模式，KL亚型有望实现从难治类型向可干预靶点的转变，这些进展共同为KL亚型的未来治疗开发提供了理论依据与明确方向。

关键词: 肺肿瘤, 基因, ras, 肿瘤微环境, 免疫疗法, STK11基因

Abstract:

The co-mutation of KRAS and STK11 （also known as LKB1） defines a distinct molecular subtype （KL subtype） in lung cancer，which is characterized by an "immunological paradox" — the coexistence of a high tumor mutation burden and primary resistance to immune checkpoint inhibitors. This resistance of this subtype mainly stems from the immunosuppressive microenvironment established by multiple mechanisms，including aberrant recruitment of myeloid cells，metabolic reprogramming，and synergistic interactions with the KEAP1/NRF2 pathway. Current therapeutic strategies for the KL subtype have shifted toward multi-pronged combination interventions，such as directly targeting KRAS^G12C，modulating the immune microenvironment，and exploring emerging therapies. Although clinical translation still faces challenges including model limitations，tumor heterogeneity，and combination-related toxicities，the integration of multi-omics analysis，innovative trial design，and novel therapeutic modalities holds promise for transforming the KL subtype from a treatment-refractory entity into a tractable therapeutic target. These advances collectively provide a theoretical foundation and clear direction for future therapeutic development targeting this specific subtype.

Key words: Lung neoplasms, Genes, ras, Tumor microenvironment, Immunotherapy, STK11 gene

高密, 干葵, 朱军, 黄美金. 肺癌中KRAS/STK11共突变亚型的两面性：免疫学悖论与治疗机遇[J]. 国际肿瘤学杂志, 2026, 53(10): 628-634.

Gao Mi, Gan Kui, Zhu Jun, Huang Meijin. Duality of KRAS/STK11 co-mutation subtype in lung cancer：immunological paradox and therapeutic opportunities[J]. Journal of International Oncology, 2026, 53(10): 628-634.

图/表 2

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肺癌中KRAS/STK11共突变亚型的两面性：免疫学悖论与治疗机遇

Duality of KRAS/STK11 co-mutation subtype in lung cancer：immunological paradox and therapeutic opportunities

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