Triparna Sen, PhD

Cecilia Brown

Lung Cancers Today

Triparna Sen, PhD, who is an associate professor in the Department of Oncological Sciences and the director of the Lung Cancer PDX Platform at the Icahn School of Medicine at Mount Sinai, joined Lung Cancers Today at the <a href="https://www.lungcancerstoday.com/conference/2025-american-society-of-clinical-oncology-annual-meeting" target="_blank" rel="noopener">2025 American Society of Clinical Oncology (ASCO) Annual Meeting.</a>Dr. Sen shared insights from her research on the immune landscape of small cell lung cancer and her presentation titled &ldquo;<a href="https://ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.8091" target="_blank" rel="noopener">Unveiling drivers of MHC repression and therapeutic strategies to counter immune evasion in small cell lung cancer</a>.&rdquo;It&rsquo;s critical to understand the immune landscape of small cell lung cancer (SCLC) because the disease &ldquo;evades anti-tumor immunity&rdquo; by suppressing MHC-I and antigen presentation, but the variability of MHC repression across molecular subtypes is &ldquo;not fully understood,&rdquo; Dr. Sen and colleagues outlined in the abstract presented at ASCO 2025.To gain a better understanding of the immune landscape of SCLC, they conducted molecular profiling on 944 SCLC and 5,056 non&ndash;small cell lung cancer (NSCLC) tumors using next-generation DNA sequencing, as well as RNA sequencing and immunohistochemistry. In addition, they conducted transcriptomic profiling of 40 SCLC cell lines and genetically engineered mouse models.Dr. Sen and colleagues identified genes that &ldquo;define immune suppression&rdquo; in SCLC and found targetable genes that can be inhibited by small molecules and evaluated the use of these inhibitors in preclinical models.&ldquo;We treated preclinical models, like cell lines and mouse models, with these inhibitors and found that when you treat these preclinical models with these inhibitors, we could reactivate the immune system,&rdquo; Dr. Sen said. &ldquo;With the reactivation of the immune system, we caused tumor regression in mice, and we also caused infiltration of CD8-positive T cells and also [saw a] decrease in exhausted T cells and upregulation of memory effector T cells.&rdquo;For example, inhibition of DNA-PKcs upregulated MHC-I, TAP1, and TAP2 and enhanced antigen-specific T-cell&ndash;mediated cytolysis in SCLC and combining the DNA-PKcs inhibitor NU1774 with anti&ndash;PD-L1 &ldquo;reactivated MHC-I and led to significant tumor regression in aggressive murine SCLC models, supporting new combination therapies.&rdquo;Dr. Sen explained that further studies will involve &ldquo;looking deeper into the mechanism&rdquo; behind what they saw in this research.&ldquo;We have preliminary indications that the innate immune response pathway may be important, but we are looking deeper into the mechanism,&rdquo; Dr. Sen said. &ldquo;The goal is to understand immune suppression better in small cell lung cancer so that we can have better targeting strategies to make immunotherapy better and further take these drugs into the clinic for small cell lung cancer.&rdquo;Advancing the understanding of SCLC biology is particularly important, Dr. Sen explained, as the heterogeneity and plasticity of SCLC make it particularly challenging to treat.&ldquo;Understanding heterogeneity and plasticity better so that we are prepared as we treat these tumors in the relapse setting could be a real game-changer,&rdquo; she said.
<div class="post-references"><h3>References</h3>American Society of Clinical Oncology 2025 Annual Meeting. <a href="https://meetings.asco.org/abstracts-presentations/249077">Abstract No. 8091</a>
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At ASCO 2025, Triparna Sen, PhD, of the Icahn School of Medicine at Mount Sinai, presented research on small cell lung cancer and genes driving immune evasion.