Zoey Chen

PhD student @MDA_UTHGrad

[Humam Kadara @humam_kadara]

Very excited to have our work on spatial profiling of lung precursor lesions and invasive lung cancers out in @Cancer_Cell. This work was done in joint collaboration with @IamLinghua and closely with many esteemed groups. Here is a run down of our major findings!

We studied multiple cohorts of normal lung tissues, precursor/preinvasive lesions and invasive lung cancer by multiple single-cell and spatial profiling modalities. We first find that invasive lung cancers, naturally, have more complex spatial expression patterns than their premalignant counterparts.

Phylogenetic reconstruction using our spatial transcriptomics analysis found that the earliest clones mapped to reactive pneumocytes, the histological resemblant of KRT8+ alveolar cells (KACs)/intermediates! This was super exciting! We previously reported that these transitional cells were not so transitional, they were stuck in limbo and acted as progenitors of lung adenocarcinoma.

KACs displayed spatial metaprograms that were distinct from normal alveolar cells and that were closely related to premalignant lesions. Remarkably, KACs had uniquely high expression of 'drivers' of inflammation (IL1R1) and were present in niches that were rich with IL1B high myeloid (macrophages) cells.

This epithelial-proinflammatory niche was disease stage-specific. Unlike oncogenic properties which we believe accumulate over the lifetime of the lesion, these niches peaked in early precursor lesions and faded in more advanced stages.

We functionally validated these KAC/epithelial-proinflammatory niches in lung carcinogenesis models showing that IL-1b treatment or co-culture with interstitial macrophages act as mitogens for KRT8+ high alveolar cells.

Importantly, there is preclinical value (and certainly clinical) value for our findings. We found that targeting IL-1B by neutralizing antibodies, including when combined with PD-1 blockade, was effective in preventing formation of precancerous lesions and their progression to adenocarcinomas. These effects were associated with reduced abundance of KACs!

Inflammation appears to be operative in the earliest stages of lung adenocarcinoma development and likely drives oncogenesis of alveolar intermediate cells that function in tissue homeostasis/remodeling after injury. Indeed, it is long thought that tumors are wounds that do not heal, and it is in this healing process if chronic where the budding tumor can hijack inherent properties in the lung. It is also plausible that targeting inflammation is valuable for intercepting lung cancer rather than treating the disease in advanced stages. This supposition is supportive of earlier clinical studies with the IL-1B antibody canakinumab (CANTOS).

Very proud of Fuduan Peng joint fellow with the Wang group, now director extraordinaire @Squirrel_PhD, talented student @Yibo_Dai for leading this work, with strong earlier effort from @warapen. I am grateful for collaborations with many groups that I personally learned so much from. This work could not have been done without funding from @NIH @theNCI (NIH funding is important!), @CPRITTexas and @LUNGevity. Also thanks to the astute reviewers as well as the editors @Cancer_Cell who helped us improve our work. #lungcancer #endcancer @MDAndersonNews

https://t.co/YO15Wsrlpc

[Zahraa Rahal @ZahraaRahal]

(1/9) Thrilled and honored to share our @NatRevClinOncol comprehensive review dissecting the crosstalk between non-small-cell lung cancer (NSCLC) and its tumour microenvironment (TME), and how it drives progression & response to therapy. ➡️ https://t.co/ClBWpXyZRy

[Zoey Chen @MYZoey4]

@MoghaddamSeyed @MDAndersonNews @MDA_UTHGrad @atstoa Congratulations Peyman!!!!!

[Humam Kadara @humam_kadara]

Excited to start studying #precancer and #cancer ecosystems with this new toy #Xenium in the lab

[Zahraa Rahal @ZahraaRahal]

Check out our piece in @Cancer_Cell👇🏻. We contextualize Liu et al.’s research https://t.co/sQuXj3mW0x on the intratumor MYCObiome 🍄 and its role in lung 🫁 cancer progression, through the lens of @humam_kadara’s lab, and suggest future research avenues.

[Zoey Chen @MYZoey4]

@humam_kadara @MDAndersonNews Congratulations!!!!

[Zoey Chen @MYZoey4]

Time flies so fast… In the past two months, I have been rotating in Dr. Kendra Carmon’s lab identifying small molecule inhibitors and antibody-drug conjugates targeting GPR56 and its signaling. I am so glad to get to know these wonderful people and work together with them!