scholarly journals The Abscopal Effect: Could a Phenomenon Described Decades Ago Become Key to Enhancing the Response to Immune Therapies in Breast Cancer?

Breast Care ◽  
2020 ◽  
Vol 15 (5) ◽  
pp. 443-449
Author(s):  
Hans-Christian Kolberg ◽  
Oliver Hoffmann ◽  
René Baumann
Keyword(s):  
Breast Cancer ◽  
Immune Response ◽  
Checkpoint Inhibitors ◽  
Immune Therapy ◽  
Antitumor Immune Response ◽  
Abscopal Effect ◽  
Antitumor Effects ◽  
Effective Combination ◽  
Immunological Mechanisms ◽  
Immune Therapies

Background: The term “abscopal effect” was defined in 1953. In oncology the term is used to describe systemic antitumor effects triggered by local irradiation (nontarget effect). Although the mechanism of the abscopal effect is not completely understood yet, it has been demonstrated that in situ tumor vaccination, and the resulting antitumor immune response, is one of the key factors. Summary: The development of immune therapies has recently led to concepts combining local radiotherapy and immune therapy with the aim of enhancing the response to immune therapy by the immunological mechanisms summarized in the term abscopal effect. This concept has also been investigated in less immunogenic tumors such as breast cancer. Initial data are promising but the hypothesis that the combination of checkpoint inhibitors and local radiotherapy could be an effective combination in breast cancer has to be proven by ongoing trials. Substitution of local radiotherapy by local hyperthermia could be an option in selected cases. Key Messages: Combination of checkpoint inhibitors with local radiation or hyperthermia in breast cancer is a promising approach and could enhance the response rates generated by immune therapy alone through the antitumor immune response initiated by the abscopal effect.

scholarly journals Immune System Efficiency in Cancer and the Microbiota Influence

Pathobiology ◽  
2021 ◽  
pp. 1-17
Author(s):  
Ana Margarida Barbosa ◽  
Alexandra Gomes-Gonçalves ◽  
António G. Castro ◽  
Egídio Torrado
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Immune Checkpoint Inhibitors ◽  
Therapeutic Response ◽  
Checkpoint Inhibitors ◽  
Critical Role ◽  
Antitumor Immune Response ◽  
System Efficiency ◽  
Novel Targets ◽  
Cancer Immunosurveillance

The immune system plays a critical role in preventing cancer development and progression. However, the complex network of cells and soluble factor that form the tumor microenvironment (TME) can dictate the differentiation of tumor-infiltrating leukocytes and shift the antitumor immune response into promoting tumor growth. With the advent of cancer immunotherapy, there has been a reinvigorated interest in defining how the TME shapes the antitumor immune response. This interest brought to light the microbiome as a novel player in shaping cancer immunosurveillance. Indeed, accumulating evidence now suggests that the microbiome may confer susceptibility or resistance to certain cancers and may influence response to therapeutics, particularly immune checkpoint inhibitors. As we move forward into the age of precision medicine, it is vital that we define the factors that influence the interplay between the triad immune system-microbiota-cancer. This knowledge will contribute to improve the therapeutic response to current approaches and will unravel novel targets for immunotherapy.

scholarly journals Breast Cancer Immunotherapy: An Update

2018 ◽  
Vol 12 ◽  
pp. 117822341877480 ◽  
Author(s):  
Issam Makhoul ◽  
Mohammad Atiq ◽  
Ahmed Alwbari ◽  
Thomas Kieber-Emmons
Keyword(s):  
Breast Cancer ◽  
Immune Response ◽  
Monoclonal Antibodies ◽  
Immune System ◽  
Cancer Vaccines ◽  
Checkpoint Inhibitors ◽  
Cancer Surveillance ◽  
Cancer Disease ◽  
Immune Attack

The immune system plays a major role in cancer surveillance. Harnessing its power to treat many cancers is now a reality that has led to cures in hopeless situations where no other solutions were available from traditional anticancer drugs. These spectacular achievements rekindled the oncology community’s interest in extending the benefits to all cancers including breast cancer. The first section of this article reviews the biological foundations of the immune response to different subtypes of breast cancer and the ways cancer may overcome the immune attack leading to cancer disease. The second section is dedicated to the actual immune treatments including breast cancer vaccines, checkpoint inhibitors, monoclonal antibodies, and the “unconventional” immune role of chemotherapy.

scholarly journals Combining PARP inhibition, radiation, and immunotherapy: A possible strategy to improve the treatment of cancer?

2018 ◽  
Vol 19 (12) ◽  
pp. 3793 ◽  
Author(s):  
Mathieu Césaire ◽  
Juliette Thariat ◽  
Serge M. Candéias ◽  
Dinu Stefan ◽  
Yannick Saintigny ◽  
...  
Keyword(s):  
Immune Response ◽  
Radiation Therapy ◽  
T Lymphocytes ◽  
Ionizing Radiation ◽  
Cytotoxic T Lymphocytes ◽  
Tumor Antigens ◽  
Checkpoint Inhibitors ◽  
Parp Inhibitors ◽  
Antitumor Immune Response ◽  
Parp Inhibition

Immunotherapy has revolutionized the practice of oncology, improving survival in certain groups of patients with cancer. Immunotherapy can synergize with radiation therapy, increase locoregional control, and have abscopal effects. Combining it with other treatments, such as targeted therapies, is a promising means of improving the efficacy of immunotherapy. Because the value of immunotherapy is amplified with the expression of tumor antigens, coupling poly(ADP-ribose) polymerase (PARP) inhibitors and immunotherapy might be a promising treatment for cancer. Further, PARP inhibitors (PARPis) are being combined with radiation therapy to inhibit DNA repair functions, thus enhancing the effects of radiation; this association might interact with the antitumor immune response. Cytotoxic T lymphocytes are central to the antitumor immune response. PARP inhibitors and ionizing radiation can enhance the infiltration of cytotoxic T lymphocytes into the tumor bed, but they can also enhance PD-1/PDL-1 expression. Thus, the addition of immune checkpoint inhibitors with PARP inhibitors and/or ionizing radiation could counterbalance such immunosuppressive effects. With the present review article, we proposed to evaluate some of these associated therapies, and we explored the biological mechanisms and medical benefits of the potential combination of radiation therapy, immunotherapy, and PARP inhibitors.

scholarly journals Immunological Basis of Genesis of Hepatocellular Carcinoma: Unique Challenges and Potential Opportunities through Immunomodulation

Vaccines ◽  
2020 ◽  
Vol 8 (2) ◽  
pp. 247 ◽  
Author(s):  
Kumar Jayant ◽  
Nagy Habib ◽  
Kai W. Huang ◽  
Mauro Podda ◽  
Jane Warwick ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Immune Response ◽  
Checkpoint Inhibitors ◽  
Contemporary Literature ◽  
Tumour Microenvironment ◽  
Vital Role ◽  
Immunological Mechanisms ◽  
Intent To Treat ◽  
In Situ Vaccine

A majority of hepatocellular carcinoma (HCC) develops in the setting of persistent chronic inflammation as immunological mechanisms have been shown to play a vital role in the initiation, growth and progression of tumours. The index review has been intended to highlight ongoing immunological changes in the hepatic parenchyma responsible for the genesis and progression of HCC. The in-situ vaccine effect of radiofrequency (RF) is through generation tumour-associated antigens (TAAs), following necrosis and apoptosis of tumour cells, which not only re-activates the antitumour immune response but can also act in synergism with checkpoint inhibitors to generate a superlative effect with intent to treat primary cancer and distant metastasis. An improved understanding of oncogenic responses of immune cells and their integration into signaling pathways of the tumour microenvironment will help in modulating the antitumour immune response. Finally, we analyzed contemporary literature and summarised the recent advances made in the field of targeted immunotherapy involving checkpoint inhibitors along with RF application with the intent to reinstate antitumour immunity and outline future directives in very early and early stages of HCC.

scholarly journals AGE-RELATED FEATURES OF SYSTEMIC ANTITUMOR IMMUNE RESPONSE IN PATIENTS WITH PRIMARY OPERABLE BREAST CANCER AND CANCER OF THE ORAL MUCOSA

2020 ◽  
Vol 19 (1) ◽  
pp. 81-88
Author(s):  
A. I. Chertkova ◽  
T. N. Zabotina ◽  
V. T. Tsiklauri ◽  
E. N. Zakharova ◽  
D. V. Tabakov ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Immune Response ◽  
T Cells ◽  
Oral Mucosa ◽  
Young Patients ◽  
Operable Breast Cancer ◽  
Antitumor Immune Response ◽  
Patients With Cancer ◽  
Age Related ◽  
Primary Operable Breast Cancer

Introduction. Age is considered as an important clinical and pathological factor in cancer patients. Malignant tumors are more likely to develop in older people, but the disease is less aggressive than in young patients. According to various authors, the influence of age on the development of tumors largely depends on the age-related features of the immune system.The aim of the present study was to determine the relationship of indicators of systemic antitumor immune response with the age of patients with primary operable breast cancer and cancer of the oral mucosa.Materials and methods. The study included patients with all subtypes of primary-operable breast cancer (n = 145) and patients with cancer of the oral mucosa (n = 29). Immunophenotyping of peripheral blood lymphocytes was performed using a wide panel of monoclonal antibodies to markers of adaptive and innate immunity cells.Results. In elder patients (40 years and older) with primary-operable breast cancer, the percentage of activated CD25+ lymphocytes and CD4+CD25+ and CD3+CD4+ T cells, NKT cells, activated HLA-DR+ lymphocytes, including activated CD3+HLA-DR+ T cells before treatment, was statistically significantly higher than in patients younger than 40 years. Patients of this group showed increase of CD8+CD - 11b+CD28– CTLs and a decrease in the number of naive lymphocytes (CD4 – CD62L+ and CD8+CD11b – CD28+) in comparison with control percentage, and the downward trend in CD4+CD25+CD127– Treg, with increased numbers of CD4+CD25+ T cells. In patients with cancer of the oral mucosa, an increase in the number of cells of some populations of the immune effector link and a decrease in the number of suppressor lymphocytes were revealed with age.Conclusion. The results suggest that age-related differences in the state of systemic antitumor immune response contribute to a more favorable course of breast cancer and some other malignancies in older persons. It is obvious that the features of age differences in the immune response to the tumor should be taken into account when prescribing systemic therapy, including immunotherapy.All patients gave written informed consent to participate in the study

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