134 Program for Research in Science and Engineering Engineering Immune Defense Hubs for Cancer Immunotherapies

Authors:

Julianne Wu, Jackson Weir, Fei Chen

Date Created:

2025-01-01

Course Title:

Professor:

Not specified

About Paper:

Immunotherapies modify a patient’s immune cells to strengthen formation, organization, and evolution of immune niches within recognition of tumor-specific antigens, reverse T-cell exhaustion, tumors. We first identified candidate ligands spatially associated and enhance attacks against malignant cells. While with intratumoral immune hub formation by inferring cytokine immunotherapies have achieved clinical success in several cancer expression from transcriptional profiles. We are characterizing types, they continue to struggle in solid tumors. Existing strategiesw these molecules may influence expression signatures within largely focus on improving the interactions between individual distinct cell populations in primary patient tissues using single- immune and cancer cells, often overlooking broader dynamics cell RNA sequencing. Furthermore, to test these ligands in vivo, between the immune system and the tumor microenvironment. we developed a scalable lentiviral delivery system to artificially Some cancer tissues possess ectopic tertiary lymphoid structures induce immune hub formation. Using a combinatorial screen, (TLSs): organized aggregations of immune cells that form we aim to identify “programs” of signaling molecules that shape under chronic inflammation. These lymphoid niches are thought immune structure formation and diversity. We designed a dual- to prime naïve T cells and reactivate effector T cells, and expression lentiviral vector, cloned constructs with several ligand they are correlated with improved patient outcomes. Current combinations, validated expression withimmunofluorescence, and studies primarily use observational approaches to probe into produced lentiviral particles for in vivo testing. Ultimately, as the intrinsic programs regulating immune cell states, but they we extend these studies into mouse models, we aim to decode lack the spatial resolution to capture multicellular interactions the ligand systems that dictate immune organization in tumors, or tissue architecture. Thus, we are developing a platform to enabling the rational design of synthetic immune circuits and test combinations of cytokines and chemokines that govern the engineered niches for cancer immunotherapies.

Abstract:

Immunotherapies modify a patient’s immune cells to strengthen formation, organization, and evolution of immune niches within recognition of tumor-specific antigens, reverse T-cell exhaustion, tumors. We first identified candidate ligands spatially associated and enhance attacks against malignant cells. While with intratumoral immune hub formation by inferring cytokine immunotherapies have achieved clinical success in several cancer expression from transcriptional profiles. We are characterizing types, they continue to struggle in solid tumors. Existing strategiesw these molecules may influence expression signatures within largely focus on improving the interactions between individual distinct cell populations in primary patient tissues using single- immune and cancer cells, often overlooking broader dynamics cell RNA sequencing. Furthermore, to test these ligands in vivo, between the immune system and the tumor microenvironment. we developed a scalable lentiviral delivery system to artificially Some cancer tissues possess ectopic tertiary lymphoid structures induce immune hub formation. Using a combinatorial screen, (TLSs): organized aggregations of immune cells that form we aim to identify “programs” of signaling molecules that shape under chronic inflammation. These lymphoid niches are thought immune structure formation and diversity. We designed a dual- to prime naïve T cells and reactivate effector T cells, and expression lentiviral vector, cloned constructs with several ligand they are correlated with improved patient outcomes. Current combinations, validated expression withimmunofluorescence, and studies primarily use observational approaches to probe into produced lentiviral particles for in vivo testing. Ultimately, as the intrinsic programs regulating immune cell states, but they we extend these studies into mouse models, we aim to decode lack the spatial resolution to capture multicellular interactions the ligand systems that dictate immune organization in tumors, or tissue architecture. Thus, we are developing a platform to enabling the rational design of synthetic immune circuits and test combinations of cytokines and chemokines that govern the engineered niches for cancer immunotherapies.

Source:

Harvard / Olivia Wright, Krithika Badarinath, Ramesh Shivdasani / 2025

Topics:

immune, cell, cancer, tumor, immunotherapy, formation, ligand, expression, program, patient, niche, tissue

Co-authors:

@juliannewu381 , @jacksonweir382 , @feichen383