Abstract PO-022: Distinct intratumoral microbiome signatures enrichment in patients with different Anaplaplastic Large Cell Lymphoma (ALCL) subtypes
Authors: Ghione Paola , Steven Horwitz , Cordeiro Peter , Arcila Maria , Galasso Natasha , Dogan Ahmet , Salles Gilles , Vanderbilt Chad 
Published: June 2024

Abstract
Background: The intratumoral microbiome is a tumor-specific component of the tumor microenvironment (TME), including microorganisms localized inside and around cancer cells and immune cells (Nejman Science2020), which was recently added to the “Hallmarks of Cancer” (Hanahan, Cancer Discovery 2022). Specific intratumoral microbiome signatures (IMS) can be detected using our targeted sequencing platform Memorial Sloan Kettering Integrated Mutation Profiling of Actionable Cancer Targets (MSK-IMPACT) (Prashkin Nat Comm 2023) data through the implementation of a specific bioinformatic pipeline (Vanderbilt J Mol Diagn 2022, Abate Ann Surg 2022). In lymphoma, where antigen stimulation is known to promote lymphomagenesis, studying the intratumoral microbiome might inform lymphoma biology and potentially new treatment strategies. In anaplastic large cell lymphoma (ALCL), a specific histologic phenotype can be found in a very diverse spectrum of diseases, ranging from smoldering lymphomas such as breast-implant associated (BIA-ALCL) and primary cutaneous (pcALCL) to systemic aggressive lymphomas such as ALK-positive or ALK-negative ALCL. We hypothesized that the different IMS might be present in different ALCL clinical presentations.
Methods: We used metagenomic techniques to analyze IMS on MSK-IMPACT-HEME as previously described (Vanderbilt J Mol Diagn 2022) of patients with ALCL in our lymphoma database. All patients signed informed consent. We calculated the odds ratio (OR) of each intra-lymphoma IMS in one ALCL subtype compared to that of the same IMS in the other ALCL subtypes. We used several different analyses to process the data for commensals and contaminants. In this regard, we built a database of potentially pathogenic or commensal microorganisms integrated in the decontam (R package) pipeline dataset. For BIA-ALCL, we compared the IMS results with those of known components of explanted textured implant biofilm.
Results: We re-analyzed the MSK-IMPACT-HEME BAM files of 58 patients with ALCL, including 12 BIA-ALCL, 11 pcALCL, and 35 systemic ALK+/- ALCL. After reviewing the data for commensals and contaminants, we could identify more than one potentially lymphoma-specific or site-specific microorganism in pcALCL (n=2) and in BIA-ALCL (n=14) (slow-growing subtypes) compared with systemic ALCL. Fewer differences were noted between pcALCL and BIA-ALCL; however, Achromobacter and Rothia were significantly enriched in BIA-ALCL compared to systemic ALCL and pcALCL (OR 14.9 p=0.001; OR=5, p=0.025) and Micromonospora in pcALCL compared to BIA-ALCL and systemic ALCL (OR=5.5, p=0.05). No specific IMS was found in systemic ALCL, as the only potentially enriched IMS (Delftiae) is likely a contaminant.
Conclusions: This analysis of IMS using targeted sequencing data, highlighted some possible associations between intratumoral microorganisms and lymphoma-specific subtypes, especially in indolent subtypes of ALCL (BIA- and pc-) compared to systemic ALCL. Further analyses with more cases and confirmatory techniques might confirm these initial findings.
Citation Format: Paola Ghione, Horwitz Steven, Peter Cordeiro, Maria Arcila, Natasha Galasso, Ahmet Dogan, Gilles Salles, Chad Vanderbilt. Distinct intratumoral microbiome signatures enrichment in patients with different Anaplaplastic Large Cell Lymphoma (ALCL) subtypes [abstract]. In: Proceedings of the Fourth AACR International Meeting on Advances in Malignant Lymphoma: Maximizing the Basic-Translational Interface for Clinical Application; 2024 Jun 19-22; Philadelphia, PA. Philadelphia (PA): AACR; Blood Cancer Discov 2024;5(3_Suppl):Abstract nr PO-022.