Systemic Immunity is Required for Effective Cancer Immunotherapy

By M. Spitzer, Y. Carmi, Nathan E. Reticker-Flynn, S. Kwek, Deepthi Madhireddy, M. Martins, P. Gherardini, Tyler R. Prestwood, Jonathan Chabon, Sean Bendall and 3 more. Cell, 2017

882 citations recorded by the source corpus.

Summary Immune responses involve coordination across cell types and tissues. However, studies in cancer immunotherapy have focused heavily on local immune responses in the tumor microenvironment. To investigate immune activity more broadly, we performed an organism-wide study in genetically-engineered cancer models using mass cytometry. We analyzed immune responses in several tissues after immunotherapy by developing intuitive models for visualizing single-cell data with statistical inference. Immune activation was evident in the tumor and systemically shortly after effective therapy was administered. However, during tumor rejection, only peripheral immune cells sustained their proliferation. This systemic response was coordinated across tissues and required for tumor eradication in several immunotherapy models. An emergent population of peripheral CD4 T cells conferred protection against new tumors and was significantly expanded in patients responding to immunotherapy. These studies demonstrate the critical impact of systemic immune responses that drive tumor rejection.

Subfields: Immunology, Oncology

View Paper: https://www.semanticscholar.org/paper/458feed6550f31eed1621b4390107f961bb962a9

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Immunology

In Oncology

Citations in the corpus

Machine Learning Identifies Stemness Features Associated with Oncogenic Dedifferentiation (2018, background): “This approach was motivated by recent observations that activation of peripheral CD4+ T cells triggered by immunotherapy is responsible for the speciﬁc killing of tumor cells (Spitzer et al., 2017).”
Defining T cell states associated with response to checkpoint immunotherapy in melanoma (2018, positive): “Surprisingly, we found that CD 8_5 T cells, which were predominantly found in post-therapy tumor samples, hardly share TCRs with the baseline sample, suggesting that members of the CD8_5 cluster are generated outside of the tumor and subsequently migrate to the tumor, consistent with observations fr”
Distinct cellular mechanisms underlie anti-CTLA-4 and anti-PD-1 checkpoint blockade (2017, positive): “Such insights will inform the rational design of combinatorial approaches, particularly given the fundamental understanding that CD4 help is critical for the development of robust T cell responses, as well as recent findings that CD4 T cells are critical for effective immunotherapy (Spitzer et al., ”
mRNA-based therapeutics: powerful and versatile tools to combat diseases (2022, background): “The treatment strategies of ICBs are widely exploited to break immune tolerance, including anti-PD-1 antibodies,(366) anti-CTLA-4 antibodies,(375) and PD-L1 siRNA.(376) Unlike ICBs, natural killer (NK) cells may be favorable for overcoming the tolerance mechanism, which is related to NK cells elimin”
Revisiting the role of CD4+ T cells in cancer immunotherapy—new insights into old paradigms (2020, neutral): “tissues during an active anti-tumour response to adjuvant therapy [42], in a study conducted in the Py-MMTV mouse”
The Influence of the Gut Microbiome on Cancer, Immunity, and Cancer Immunotherapy. (2018, background): “Recent evidence substantiates the need for preserved overall systemic immunity in mediating responses to immunotherapy specifically (Chen and Mellman, 2013, 2017; Spitzer et al., 2017).”
Pan-cancer single-cell landscape of tumor-infiltrating T cells (2021, background): “Taken together, potentially tumor-reactive T cells emerged—TFH/TH1 cells, TNFRSF9 + Treg cells, CD8 ISG T cells, and four Tex cell populations, representing a local antitumor immune response—whereas the expanded CD8 Temra cells might also harbor tumor-specific TCRs, which is consistent with the noti”