Immunotherapy plus cryotherapy

Potential augmented abscopal effect for advanced cancers

Joe Abdo, David L. Cornell, Sumeet K. Mittal, Devendra K. Agrawal

Research output: Contribution to journalReview article

4 Citations (Scopus)

Abstract

Since the 1920s the gold standard for treating cancer has been surgery, which is typically preceded or followed with chemotherapy and/or radiation, a process that perhaps contributes to the destruction of a patient's immune defense system. Cryosurgery ablation of a solid tumor is mechanistically similar to a vaccination where hundreds of unique antigens from a heterogeneous population of tumor cells derived from the invading cancer are released. However, releasing tumor-derived self-antigens into circulation may not be sufficient enough to overcome the checkpoint escape mechanisms some cancers have evolved to avoid immune responses. The potentiated immune response caused by blocking tumor checkpoints designed to prevent programmed cell death may be the optimal treatment method for the immune system to recognize these new circulating cryoablated self-antigens. Preclinical and clinical evidence exists for the complementary roles for Cytotoxic T-lymphocyte-associated protein (CTLA-4) and PD-1 antagonists in regulating adaptive immunity, demonstrating that combination immunotherapy followed by cryosurgery provides a more targeted immune response to distant lesions, a phenomenon known as the abscopal effect. We propose that when the host's immune system has been "primed" with combined anti-CTLA-4 and anti-PD-1 adjuvants prior to cryosurgery, the preserved cryoablated tumor antigens will be presented and processed by the host's immune system resulting in a robust cytotoxic CD8+ T-cell response. Based on recent investigations and well-described biochemical mechanisms presented herein, a polyvalent autoinoculation of many tumor-specific antigens, derived from a heterogeneous population of tumor cancer cells, would present to an unhindered yet pre-sensitized immune system yielding a superior advantage in locating, recognizing, and destroying tumor cells throughout the body.

Original languageEnglish (US)
Article number85
JournalFrontiers in Oncology
Volume8
Issue numberMAR
DOIs
StatePublished - Mar 28 2018

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Cryotherapy
Immunotherapy
Immune System
Neoplasms
Cryosurgery
Autoantigens
Neoplasm Antigens
Cytotoxic T-Lymphocytes
Adaptive Immunity
Population
Vaccination
Cell Death
Radiation
T-Lymphocytes
Antigens
Drug Therapy

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Immunotherapy plus cryotherapy : Potential augmented abscopal effect for advanced cancers. / Abdo, Joe; Cornell, David L.; Mittal, Sumeet K.; Agrawal, Devendra K.

In: Frontiers in Oncology, Vol. 8, No. MAR, 85, 28.03.2018.

Research output: Contribution to journalReview article

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