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The Biology of Immune-Active Cancers and Their Regulatory Mechanisms

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Tumor Microenvironment

Part of the book series: Cancer Treatment and Research ((CTAR,volume 180))

Abstract

The development of cancer results from the evolutionary balance between the proliferating aptitude of cancer cells and the response of the host’s tissues. Some cancers are characterized by genetic instability dependent upon impaired DNA repair mechanisms that lead to the chaotic disruption of multiple cellular functions often in excess of the cancer survival needs and may exert broad effects on surrounding tissues, some beneficial and some detrimental to cancer growth. Among them, inflammatory processes that accompany wound healing may initiate a reaction of the host against the neo-formation. This is possibly triggered by the release by dying cancer cells of molecules known as Damage-Associated Molecular Patterns (DAMPs) following a process termed Immunogenic Cell Death (ICD) that initiates an immune response through innate and adaptive mechanisms. Indeed, analysis of large cancer data sets has shown that ICD is strictly associated with the activation of other immune effector or immune-regulatory pathways. Here, we will describe how immune activation and compensatory immune-regulatory mechanisms balance anti-cancer immune surveillance and the roles that innate and adaptive immunity play including the weight that neo-epitopes may exert as initiators and sculptors of high-affinity memory and effector immune responses against cancer. We will discuss the evolutionary basis for the existence of immune checkpoints and how several theories raised to explain cancer resistance to immunotherapy represent a facet of a similar evolutionary phenomenon that we described in the Theory of Everything. We will show how the biology of immunogenicity and counterbalancing immune regulation is widespread across cancers independent of their ontogenesis while subtle idiosyncratic differences are discernible among them. Finally, we will suggest that overcoming immune resistance implies distinct approaches relevant to the immune context of individual cancers.

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Notes

  1. 1.

    In bold are transcripts in common between the ICR and the TIS signature.

Abbreviations

ACT :

Adoptive Cell Therapy

CIR :

Cancer Immune Responsiveness

CIT :

Checkpoint Inhibitor Therapy

DAMPs :

Damage-Associated Molecular Patterns

DSP :

Digital Spatial Profiling

HMGB1 :

High Mobility Group Box 1

ICD :

Immunogenic Cell Death

ICR :

Immunologic Constant of Rejection

IDO :

Indoleamine 2,3-Dioxygenase

IFN :

Interferon

IL :

Interleukin

IO :

Immune Oncology

NOS :

Nitric Oxide Synthase

PDL1 :

Programmed Cell Death Protein Ligand 1

TCGA :

The Cancer Genome Atlas

TGF :

Transforming Growth Factor

TILs :

Tumor-Infiltrating Lymphocytes

TIM-3/HAVCR2 :

T cell Immunoglobulin and Mucin-domain containing-3/Hepatitis A Virus Cellular Receptor 2

TIS :

Tumor Inflammation Signature

TMB :

Tumor Mutational Burden

TME :

Tumor Micro-environment

TOC :

Two Option Choice

TOE :

Theory Of Everything

VEGF :

Vascular Endothelial Growth Factor

VISTA :

V-domain Immunoglobulin Suppressor of T cell Activation

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Authors and Affiliations

  1. Sidra Research, Doha, Qatar

    Davide Bedognetti

  2. Essa Pharma, South San Francisco, CA, 94080, USA

    Alessandra Cesano

  3. Refuge Biotechnologies, Menlo Park, CA, 94025, USA

    Francesco M. Marincola

  4. Allogene, South San Francisco, CA, 94080, USA

    Ena Wang

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  1. Davide Bedognetti
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  2. Alessandra Cesano
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  3. Francesco M. Marincola
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  4. Ena Wang
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Correspondence to Ena Wang .

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Editors and Affiliations

  1. Department of Immuno-Oncology, City of Hope National Medical Center, Duarte, CA, USA

    Peter P. Lee

  2. Refuge Biotechnologies, Menlo Park, CA, USA

    Francesco M. Marincola

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Bedognetti, D., Cesano, A., Marincola, F.M., Wang, E. (2020). The Biology of Immune-Active Cancers and Their Regulatory Mechanisms. In: Lee, P., Marincola, F. (eds) Tumor Microenvironment. Cancer Treatment and Research, vol 180. Springer, Cham. https://doi.org/10.1007/978-3-030-38862-1_5

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