# Project 2: Spatial Architecture of Tumor-Mediated Immunosuppression

> **NIH NIH U54** · STANFORD UNIVERSITY · 2020 · $372,870

## Abstract

ABSTRACT/SUMMARY – Project 2: Spatial Architecture of Tumor-Mediated Immunosuppression
Cancer progression is a disease of increasing disorder—yet a form of disorder with ordained stages of
development. Beyond the internal genomic and epigenetic events that occur to drive a cell towards outright
carcinogenesis and then metastasis, there co-exist the ordered events a cancer imposes on immune cells it
encounters on its progression towards advanced disease. Induction of tolerance, avoidance of apoptosis, and
even recruitment of the immune system to aid a tumor's growth are all poorly understood processes. We
propose to undertake deep phenotyping of the 2D and 3D architecture of the tumor-lymph node micro-
environment in human cancer & murine model counterparts —wherein it is thought that some of the initial
phases of the tumor's avoidance and recruitment mechanisms are first implemented. How is the architecture
of the immune environment disrupted in the face of tumor metastasis? Are their micro-communities changed
(as defined by particular cell-cell interactions) whose presence or absence defines clinical outcomes during
progression of the tumor? To this end we have developed a technology (ABSeq) that enables us to sensitively
and quantitatively image tumors with 60 markers per 3-5 hours (scalable to 480 in a time-dependent manner).
These markers are selected from a range of intracellular or surface epitopes (recognized by antibodies) or
RNAs. The hypothesis is that an orchestrated corruption of immune surveillance is initiated by
cancers as they progress, and that the micro-scale architecture of the lymph node (by way of which
cells are talking to whom and what broader effects occur across the lymph node and beyond) is
disrupted in a defined manner. Understanding of this process will result in mechanistic and therapeutic
insights that are unavailable by other analysis modalities. Databases of 2D and 3D microenvironments will be
publicly created and mined for associations that define the architectural changes in draining lymph nodes that
occur as tumors progress and initiate tolerance. Perturbations that include immunotherapies will be
implemented on the murine models to determine the further architectural changes that occur post therapy.
Together the information will provide a first ever deep profiling of every major immune cell subset in lymph
nodes as they re-architect themselves during metastatic establishment.

## Key facts

- **NIH application ID:** 9982082
- **Project number:** 5U54CA209971-05
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** GARRY P NOLAN
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $372,870
- **Award type:** 5
- **Project period:** — → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9982082

## Citation

> US National Institutes of Health, RePORTER application 9982082, Project 2: Spatial Architecture of Tumor-Mediated Immunosuppression (5U54CA209971-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9982082. Licensed CC0.

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