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Intrinsic features of the cancer cell as drivers of immune checkpoint blockade response and refractoriness

Chiara Ursino1, Cécile Mouric1, Laurent Gros1

  • 1Institut de Recherche en Cancérologie de Montpellier (IRCM), Inserm U1194, Univ Montpellier, Institut du Cancer de Montpellier (ICM), Montpellier, France.

Frontiers in Immunology
|May 14, 2023
PubMed

Insights

Immune checkpoint blockade shows promise in cancer treatment, but predicting patient response remains challenging. Understanding cancer cell characteristics is key to improving immunotherapy effectiveness and overcoming resistance.

Area of Science:

  • Oncology
  • Immunology
  • Cancer Biology

Background:

  • Immune checkpoint blockade (ICB) has revolutionized cancer treatment, improving survival and quality of life.
  • However, ICB benefits only a subset of patients, and predicting response is difficult.
  • Cancer cell characteristics significantly influence immunotherapy outcomes.

Purpose of the Study:

  • To review and synthesize current knowledge on the link between cancer cell traits and response to immunotherapy.
  • To explore how intra-tumor heterogeneity in lung cancer impacts sensitivity and resistance to ICB.
  • To identify specific cancer cell features associated with ICB efficacy and resistance.

Main Methods:

  • Literature review focusing on cancer cell characteristics and immunotherapy response.
  • Analysis of studies primarily in lung cancer to illustrate heterogeneity effects.
  • Synthesis of data on genomic, epigenetic, metabolic, and signaling pathways in cancer cells related to ICB.

Main Results:

  • Genomic instability, epigenetics, and innate immune signaling in cancer cells influence ICB response.
  • Altered cancer cell metabolism, oncogenic signaling, tumor suppressor loss, and cGAS/STING pathway regulation are linked to ICB resistance.
  • Cancer cell diversity within a single pathology can explain variable responses to immunotherapy.

Conclusions:

  • Cancer cell intrinsic factors are critical determinants of response to immune checkpoint blockade.
  • Understanding these factors can guide the development of predictive biomarkers and novel therapeutic strategies.
  • First-line ICB may drive the evolution of cancer cell clones and resistance mechanisms, necessitating further research.
Keywords:
adjuvanticityimmune checkpointimmunogenicitiyplasticicitytumor micro environment (TME)

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