# Predicting and profiling long-term survival after immune checkpoint inhibition

> **NIH NIH K23** · VANDERBILT UNIVERSITY MEDICAL CENTER · 2020 · $151,200

## Abstract

Project Summary
Immune checkpoint inhibitors, particularly anti-PD-1/PD-L1 (programmed cell death-1/ligand), represents an
emerging and novel therapeutic class with clinical efficacy in many cancers. As such, characterizing features
predictive of response, immune changes on therapy, and long-term clinical outcomes are critical objectives for
a large and growing population. Currently, we remain largely unable to predict individual patient benefit from
these agents. Using pre-treatment samples from patients who received anti-PD-1/PD-L1, we identified that
expression of major histocompatibility class II (MHC-II) strongly correlated with response to therapy, as well as
CD4 and CD8 T cell infiltration. Cell line studies also suggested that MHC-II expression also correlates with
pro-immune gene signatures, including pathways such as “T cell receptor signaling”, “PD-1 reactome”, and
“allograft rejection.” In a larger cohort, we will use qualitative and quantitative immunohistochemistry methods
to verify and establish the predictive value of MHC-II expression on benefit to anti-PD-1/PD-L1 (Aim 1). We will
also assess whether MHC-II may be induced by common melanoma therapeutics in vitro. Next, we will
leverage cutting edge multiplexed mass cytometry to characterize the evolving anti-tumor immune response
unleashed by anti-PD-1. Available data suggests that in anti-PD-1/PD-L1 responsive tumors, a pre-existing
immune response exists that is released by the blockade of PD-1/PD-L1. As such, we hypothesize that
peripheral and tumor infiltrating immune cells may be distinct prior to, and following treatment among treatment
responders. To achieve unprecedented longitudinal characterization of multiple evolving immune subsets, we
will perform high-dimensional multiplexed mass cytometry analysis on peripheral blood (obtained at baseline, 3
weeks, 12 weeks, 6 months after treatment) and tumor biopsies (baseline and 3 weeks) (Aim 2). Finally, while
many patients respond to anti-PD-1/PD-L1, the molecular basis, incidence, timing, and clinical characteristics
of acquired resistance are totally uncharacterized. Further, the incidence of chronic and delayed toxicities has
not been explored. We plan to collect retrospective clinical data and tumor samples on a large population of
patients who respond and then progress, and explore toxicities experienced by long-term survivors treated with
anti-PD-1/PD-L1 (Aim 3). These studies, in conjunction with internationally recognized mentors and advisors,
and a rigorous training plan, will provide the optimal conditions from which to develop an independent research
career performing high-impact patient-oriented research.

## Key facts

- **NIH application ID:** 9996509
- **Project number:** 5K23CA204726-05
- **Recipient organization:** VANDERBILT UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** Douglas B Johnson
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $151,200
- **Award type:** 5
- **Project period:** 2016-09-20 → 2021-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9996509

## Citation

> US National Institutes of Health, RePORTER application 9996509, Predicting and profiling long-term survival after immune checkpoint inhibition (5K23CA204726-05). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9996509. Licensed CC0.

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