Immuno-PET identifies the myeloid compartment as a key contributor to the outcome of the antitumor response under PD-1 blockade

Proc Natl Acad Sci U S A. 2019 Aug 20;116(34):16971-16980. doi: 10.1073/pnas.1905005116. Epub 2019 Aug 2.


Immunotherapy using checkpoint-blocking antibodies against PD-1 has produced impressive results in a wide range of cancers. However, the response remains heterogeneous among patients. We used noninvasive immuno-positron emission tomography (PET), using 89Zr-labeled PEGylated single-domain antibody fragments (nanobodies or VHHs), to explore the dynamics and distribution of intratumoral CD8+ T cells and CD11b+ myeloid cells in response to anti-PD-1 treatment in the MC38 colorectal mouse adenocarcinoma model. Responding and nonresponding tumors showed consistent differences in the distribution of CD8+ and CD11b+ cells. Anti-PD-1 treatment mobilized CD8+ T cells from the tumor periphery to a more central location. Only those tumors fully infiltrated by CD8+ T cells went on to complete resolution. All tumors contained CD11b+ myeloid cells from the outset of treatment, with later recruitment of additional CD11b+ cells. As tumors grew, the distribution of intratumoral CD11b+ cells became more heterogeneous. Shrinkage of tumors in responders correlated with an increase in the CD11b+ population in the center of the tumors. The changes in distribution of CD8+ and CD11b+ cells, as assessed by PET, served as biomarkers to gauge the efficacy of anti-PD-1 treatment. Single-cell RNA sequencing of RNA from intratumoral CD45+ cells showed that CD11b+ cells in responders and nonresponders were markedly different. The responders exhibited a dominant population of macrophages with an M1-like signature, while the CD45+ population in the nonresponders displayed an M2-like transcriptional signature. Thus, by using immuno-PET and single-cell RNA sequencing, we show that anti-PD-1 treatment not only affects interactions of CD8+ T cells with the tumor but also impacts the intratumoral myeloid compartment.

Keywords: PET imaging; checkpoint blockade; nanobodies; single-cell RNA sequencing; tumor immune microenvironment.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma* / diagnostic imaging
  • Adenocarcinoma* / immunology
  • Adenocarcinoma* / pathology
  • Adenocarcinoma* / therapy
  • Animals
  • Antigens, Neoplasm / immunology*
  • CD11b Antigen / immunology
  • CD8-Positive T-Lymphocytes* / immunology
  • CD8-Positive T-Lymphocytes* / pathology
  • Cell Line, Tumor
  • Colorectal Neoplasms* / diagnostic imaging
  • Colorectal Neoplasms* / immunology
  • Colorectal Neoplasms* / pathology
  • Colorectal Neoplasms* / therapy
  • Female
  • Mice
  • Neoplasm Proteins / immunology*
  • Neoplasms, Experimental* / diagnostic imaging
  • Neoplasms, Experimental* / immunology
  • Neoplasms, Experimental* / pathology
  • Neoplasms, Experimental* / therapy
  • Positron-Emission Tomography*
  • Programmed Cell Death 1 Receptor / immunology*
  • Tumor Microenvironment / immunology


  • Antigens, Neoplasm
  • CD11b Antigen
  • Itgam protein, mouse
  • Neoplasm Proteins
  • Pdcd1 protein, mouse
  • Programmed Cell Death 1 Receptor