Exceptional Long-term Response to Immunotherapy in an African American Man With STK11/TP53/RB1-Mutated Metastatic Lung Adenocarcinoma - Journal Article

Sep 23, 2026

Immunotherapy is standard for advanced and resectable lung cancer, yet mutations can predict resistance and durable benefit. A 68-year-old African American man with stage IIIB metastatic lung adenocarcinoma progressed after first-line carboplatin-based chemoradiotherapy. Subcarinal lymph node testing identified STK11 S216F, TP53 R273L, and RB1 splice site mutations, with high TMB (19.0/Mb) and high PD-L1 22c3 expression (TPS 70%, intensity 2+). Despite resistance associations, intravenous pembrolizumab produced an exceptional, sustained response over two years, suggesting co-mutation and biomarker context may shape ongoing effectiveness and survival equity.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages5

Reading Time13 min

AccessFree to download

Abstract

Keywords

Introduction

Case Presentation

Molecular Testing and Biomarkers

Treatment Course and Response

Exceptional Long-term Response to Immunotherapy in an African American Man With STK11/TP53/RB1-Mutated Metastatic Lung Adenocarcinoma Journal of Investigative Medicine High Impact Case Reports Volume 13: 1–5 © 2025 American Federation for Medical Research DOI: 10. 1177/23247096251346830 [journals.sagepub.com/home/hic](journals.sagepub.com/home/hic) Yaolin Zhou 1, Maneesh Gaddam2, and Sunil Badami3 Abstract Immunotherapy has become the standard of care for advanced and resectable lung cancer, and specific mutations may predict immunotherapy response. For example, STK11 mutations, which are more common in African American patients, are associated with immunotherapy resistance. A 68-year-old African American man with stage IIIB lung adenocarcinoma with mediastinal lymph node involvement progressed on first-line concurrent carboplatin-based chemoradiotherapy. Molecular testing of the patient’s subcarinal lymph node tissue revealed STK11 S216F, TP53 R273L, and RB1 splice site mutations; high tumor mutation burden (19.0 mutations/Mb); and high PD-L1 22c3 expression (TPS 70%, 2 + intensity). Treatment with carboplatin-based chemotherapy with radiation therapy failed to control the disease, but the patient has tolerated and responded well to intravenous pembrolizumab. Although STK11 mutations are associated with immunotherapy resistance, our patient demonstrated an exceptional and sustained response to immunotherapy for over two years. The patient’s STK11/TP53 co-mutation, along with high TMB and PD-L1 22c3 TPS scores, may help explain his continued responsiveness to immunotherapy and longer survival. Importantly, incorporating genetic ancestry differences in mutation prevalence and the impact of specific mutations and co-mutations, may help ensure the equitable and optimal treatment of all patients with lung cancers. Keywords lung cancer, immunotherapy, African American, STK11, co-mutations, genetic ancestry Introduction Immunotherapy, including monoclonal antibodies against programmed death-1 and programmed death ligand-1 (PDL1), has become the standard of care for both advanced andresectable lung cancer. However, approximately 20% to 27% of patients with advanced non-small cell lung cancer (NSCLC) show primary resistance to immunotherapy, and resistance to chemoimmunotherapy is about 10% .1 Specific mutations in NSCLC can influence treatment response and survival outcomes. In general, patients with STK11-mutant NSCLC tend to have lower PD-L1 expression and poorer response to immunotherapy.2,3 Recent studies suggest that the impact of STK11 may be modulated by co-mutations, tumor mutation burden (TMB) status, and PD-L1 expression, influencing both immunotherapy response and patient survival.4 For example, NSCLC patients with co-mutations in STK11 and TP53 tend to respond better to immunotherapy.4 Compared to STK11-mutated/TP53 wild-type tumors, co-mutated tumors exhibit higher TMB and exome-level neoantigen load, possibly due to accumulated DNA damage from mutated TP53, increasing immunogenicity and immunotherapy efficacy.5 1 Department of Pathology and Laboratory Medicine, Brody School of Medicine, East Carolina University, Greenville, NC, USA 2Division of Pulmonary, Critical Care and Sleep Medicine, Appalachian Regional Healthcare, Hazard, KY, USA 3Division of Hematology-Oncology in the Department of Internal Medicine, Brody School of Medicine, East Carolina University, Greenville, NC, USA Received May 5, 2025. Accepted May 16, 2025. Corresponding Author: Maneesh Gaddam, Division of Pulmonary, Critical Care and Sleep Medicine, Appalachian Regional Healthcare, 1702 Amethyst Way, Lexington, KY 40509, USA. Email: [drmaneeshgaddam@gmail.com](drmaneeshgaddam@gmail.com) Creative Commons Non Commercial CC BY-NC: This article is distributed under the terms of the Creative Commons AttributionNonCommercial 4.0 License ([https://creativecommons.org/licenses/by-nc/4.0/](https://creativecommons.org/licen

FAQs

What disease and stage are described in this case?

The case involves a 68-year-old African American man with stage IIIB lung adenocarcinoma and mediastinal lymph node involvement progressing after initial therapy.

Which genetic alterations and biomarkers were found?

Testing of subcarinal lymph node tissue showed STK11 S216F, TP53 R273L, and RB1 splice-site mutations, with high tumor mutation burden (19.0 mutations/Mb) and high PD-L1 22c3 expression (TPS 70%, intensity 2+).

How did the patient respond to pembrolizumab despite STK11-associated resistance?

Although STK11 mutations are often linked to immunotherapy resistance, the patient tolerated and responded well to intravenous pembrolizumab, with an exceptional sustained response lasting over two years.

Sep 23, 2026

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