Lung Cancer Research Progress

2024–2026 Julie Swedberg YOLO Research Award Recipient

Principal Investigator: Jessica Konen, PhD, Winship Cancer Institute of Emory University, Department of Hematology and Medical Oncology

Project Title: miR-29 as a Master Regulator of Anti-Tumor Immunity

Advancing lung cancer research means asking bold questions — especially about why some tumors respond to immunotherapy while others resist it. That’s exactly what Dr. Jessica Konen is working to solve as the 2024–2026 Julie Swedberg YOLO Research Award recipient.

Her research focuses on a powerful molecular regulator called miR-29 and how it may control the immune system’s ability to recognize and eliminate lung cancer.

Meet Dr. Jessica Konen

Dr. Konen has dedicated her scientific career to understanding tumor growth, metastasis, drug resistance, and immune evasion in non-small cell lung cancer (NSCLC).

She began her research journey at Emory University, where she studied how different tumor cell populations cooperate to invade surrounding tissue. Her work uncovered survival dependencies in highly invasive “leader” cells — findings that opened the door to potential anti-metastatic treatment strategies.

Following her PhD, Dr. Konen completed her postdoctoral training at The University of Texas MD Anderson Cancer Center, where she expanded into tumor immunology and immunotherapy research, particularly in KRAS-driven lung cancers. There, she helped identify novel mechanisms by which tumors resist immune checkpoint inhibitors — discoveries that may guide smarter combination therapies.

Now an instructor at the Winship Cancer Institute, Dr. Konen brings together her expertise in tumor biology and immunology to better understand how lung cancers escape immune detection — and how to stop them.

About the Project

What Is miR-29 — and Why Does It Matter?

miR-29 is a small regulatory molecule known as a microRNA. While small in size, it has the potential to control large networks of genes.

Dr. Konen’s project investigates how the loss of miR-29 contributes to resistance to immune checkpoint inhibitors like anti-PD-1 therapy. Her goal is to:

• Understand how miR-29 loss affects tumor cells directly

• Determine how it reshapes the tumor microenvironment

• Identify whether restoring miR-29 can reinvigorate anti-tumor immunity

• Develop rational drug combinations to improve immunotherapy outcomes

Ultimately, this work aims to uncover new biology that could lead to more effective treatment strategies for lung cancer.

July 2025 Update: Restoring miR-29 Improves Immunotherapy Response

During this reporting period, Dr. Konen’s team focused on how miR-29 influences immune cell behavior inside tumors.

Key Findings:

• Re-expressing miR-29 in mouse lung cancer models improved response to PD-1 blockade.

• Combining miR-29 expression with anti-PD-1 therapy shifted tumors toward a pro-inflammatory (anti-tumor) immune environment.

• Tumors showed:

  • Increased cytotoxic CD8+ T cells (the immune system’s cancer-killing cells)

  • Decreased suppressive monocytes (immune cells that can dampen anti-tumor responses)

Importantly, analysis of human lung adenocarcinoma datasets showed similar patterns:

• Tumors with high miR-29 levels had higher CD8 expression.

• These tumors also had lower levels of CD14, a marker associated with suppressive monocytes.

When researchers removed miR-29 from tumor cells, they observed dramatic changes in immune cell phenotypes — particularly in CD8+ T cells — suggesting that miR-29 plays a central role in orchestrating anti-tumor immunity.

Next steps included testing whether miR-29 loss directly drives resistance to anti-PD-1 therapy and identifying gene signatures that could serve as predictive biomarkers.

January 2026 Update: Confirming miR-29’s Role in Immunotherapy Resistance

In this most recent reporting period, the team deepened their mechanistic understanding of miR-29.

Using CRISPR-Cas9 gene editing, they depleted miR-29a in tumor cells and discovered:

• Loss of miR-29 was sufficient to cause resistance to anti-PD-1 therapy.

• This provides strong pre-clinical evidence that miR-29 is critical for effective immunotherapy response.

When miR-29 was reintroduced alongside anti-PD-1 therapy, the tumor immune microenvironment shifted again toward a strong anti-tumor state:

• Significant influx of cytotoxic and proliferating CD8+ T cells

• Increase in pro-inflammatory macrophages

• Elevated production of CXCL9, a molecule that attracts immune cells into tumors

The team also identified additional soluble factors influenced by miR-29 — including LPA, CD93, and CD105 — that may shape macrophage differentiation.

What’s Next?

Dr. Konen’s lab is now:

• Mapping how miR-29 directly and indirectly influences CD8+ T cells and macrophages

• Developing a miR-29-dependent gene signature to predict immunotherapy response in patients

• Designing a next-generation miR-29 mimic therapy with improved stability and tumor targeting

• Testing combination strategies pairing miR-29 restoration with immune checkpoint inhibition

These studies aim to lay the groundwork for future clinical translation.