Vincent K. Lam, MD, assistant professor, oncology, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, discusses findings from a study profiling the tumor immune microenvironment in patients with 

 fusion–positive lung cancer and potential future directions for this research.

This study, which was supported by Caris Life Science’s Precision Oncology Alliance, aimed to characterize the major immune components of the 

 fusion–positive lung cancer tumor microenvironment (TME), analyzed next-generation sequencing results from 5490 patients with non–small cell lung cancer (NSCLC) who had undergone DNA and RNA sequencing. Of these patients, 374 had 

-rearranged NSCLC. Comparators included 3169 patients with 

 fusion–positive tumors had low tumor mutational burden, (median 3.0 mut/MB vs 9.0 mut/MB and 4.0 mut/MB in the 

-mutant cohorts, respectively). This finding may partially explain why many 

 fusion–positive tumors have minimal or no responses to immune checkpoint inhibitors, despite unexpectedly high PD-L1 expression that is comparable to that in 

The second part of this study, which used bioinformatics pipelines to determine the immune contexture of 

 fusion–positive tumors, found potential targets that may help inflame the TME and thus enhance immunotherapy responses, although additional research is needed in this area, Lam notes. One such target is M2 macrophages, as M2 macrophage polarization contributes to an immunosuppressive TME, Lam explains. M2 macrophages had a median cell fraction of 7.2% in 

 fusion–positive tumors compared with 5.7% and 6.5% in

 mutated tumors, respectively. Another potential target is the CD73 adenosine pathway, which suppresses responses to immunotherapy in some tumors such as 

-mutated tumors, Lam says. In this study, CD73 expression in 

 fusion-positive tumors was similar to that of EGFR-mutated tumors and expression of adenosine receptor ADORA1 was elevated (median 11.9 vs 9.4 and 9.6 in 

-mutant cohorts, respectively). These findings demonstrate potential areas for immune modulation in 

 fusion–positive NSCLC, Lam concludes.

Videos

Vincent K. Lam, MD, discusses findings from a study profiling the tumor immune microenvironment in patients with ALK fusion–positive lung cancer and potential future directions for this research.

Dr Lam on the Tumor Microenvironment in ALK Fusion+ Lung Cancer

Vincent Lam, MD, assistant professor, The University of Texas MD Anderson Cancer, discusses agents to target ROS1-mutated non-small cell lung cancer (NSCLC). 

The agent that is furthest in development is lorlatinib which was investigated in a phase II trial. The ROS1 cohort demonstrated good response for patients who had been previously treated or were treatment-na

Vincent Lam, MD, assistant professor, The University of Texas MD Anderson Cancer, discusses agents to target ROS1-mutated non-small cell lung cancer (NSCLC).

Vincent Lam, MD

Articles

Dr Lam on the Tumor Microenvironment in ALK Fusion+ Lung Cancer

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