Targeting Antitumor Immune Response for Enhancing the Efficacy of Photodynamic Therapy of Cancer: Recent Advances and Future Perspectives

Photodynamic therapy (PDT) is a minimally invasive therapeutic strategy for cancer treatment, which can destroy local tumor cells and induce systemic antitumor immune response, whereas, focusing on improving direct cytotoxicity to tumor cells treated by PDT, there is growing interest in developing approaches to further explore the immune stimulatory properties of PDT. In this review we summarize the current knowledge of the innate and adaptive immune responses induced by PDT against tumors, providing evidence showing PDT facilitated-antitumor immunity. Various immunotherapeutic approaches on different cells are reviewed for their effectiveness in improving the treatment efficiency in concert with PDT. Future perspectives are discussed for further enhancing PDT efficiency via intracellular targetable drug delivery as well as optimized experimental model development associated with the study of antitumor immune response.

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The impact of macrophage-cancer cell interaction on the efficacy of photodynamic therapy

Photochemical & Photobiological Sciences ◽

10.1039/c4pp00451e ◽

2015 ◽

Vol 14 (8) ◽

pp. 1403-1409 ◽

Cited By ~ 15

Author(s):

Mladen Korbelik ◽

Michael R. Hamblin

Keyword(s):

Immune Response ◽

Photodynamic Therapy ◽

Tumor Cells ◽

Adaptive Immune Response ◽

Cell Interaction ◽

M1 Macrophages ◽

Adaptive Immune ◽

Light Delivery ◽

Dying Cells ◽

The Impact

PDT has different effects on macrophages in tumors. The photosensitizer (PS) is taken up by M2 TAMS inside the tumor, which are killed upon light delivery. Signaling from these dying cells attracts new M1 macrophages from the circulation that can kill remaining tumor cells and stimulate an adaptive immune response.

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Combining Oncolytic Viruses and Small Molecule Therapeutics: Mutual Benefits

Cancers ◽

10.3390/cancers13143386 ◽

2021 ◽

Vol 13 (14) ◽

pp. 3386

Author(s):

Bart Spiesschaert ◽

Katharina Angerer ◽

John Park ◽

Guido Wollmann

Keyword(s):

Immune Response ◽

Immune Responses ◽

Tumor Cells ◽

Small Molecule ◽

Antiviral Immunity ◽

Oncolytic Viruses ◽

Antitumor Immune Response ◽

Antiviral Responses ◽

Small Molecule Therapeutics ◽

Immunosuppressive Factors

The focus of treating cancer with oncolytic viruses (OVs) has increasingly shifted towards achieving efficacy through the induction and augmentation of an antitumor immune response. However, innate antiviral responses can limit the activity of many OVs within the tumor and several immunosuppressive factors can hamper any subsequent antitumor immune responses. In recent decades, numerous small molecule compounds that either inhibit the immunosuppressive features of tumor cells or antagonize antiviral immunity have been developed and tested for. Here we comprehensively review small molecule compounds that can achieve therapeutic synergy with OVs. We also elaborate on the mechanisms by which these treatments elicit anti-tumor effects as monotherapies and how these complement OV treatment.

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IMMU-44. AN IMMUNOTHERAPEUTIC VACCINE COMPOSED OF IRRADIATED WHOLE TUMOR CELLS PULSED WITH MANNAN-BAM, TLR LIGANDS AND ANTI-CD40 ANTIBODY INDUCES POTENT IMMUNE RESPONSE IN PRECLINICAL GBM ANIMAL MODEL

Neuro-Oncology ◽

10.1093/neuonc/noab196.403 ◽

2021 ◽

Vol 23 (Supplement_6) ◽

pp. vi102-vi102

Author(s):

Herui Wang ◽

Rogelio Medina ◽

Juan Ye ◽

Pashayar Lookian ◽

Ondrej Uher ◽

...

Keyword(s):

Immune Response ◽

T Cells ◽

Tumor Cells ◽

T Lymphocyte ◽

Cd8 T Cells ◽

Therapeutic Efficacy ◽

Poly I:C ◽

Control Group ◽

Complete Regression ◽

Adaptive Immune

Abstract Despite numerous therapeutic advances, the treatment of glioblastoma multiforme (GBM) remains a challenge, with current 5-year survival rates estimated at 4%. Multiple characteristic elements of GBM contribute to its treatment-resistance, including its low immunogenicity and its highly immunosuppressive microenvironment that can effectively disarm adaptive immune responses. Hence, therapeutic strategies that aim to boost T-lymphocyte mediated responses against GBM are of great therapeutic value. Herein, we present a therapeutic vaccination strategy that promotes the phagocytosis of tumor cells, enhances tumor antigen presentation, and induces a tumor-specific adaptive immune response. This strategy consists of vaccinations with irradiated whole tumor cells (rWTC) pulsed with phagocytic agonists (Mannan-BAM), TLR ligands [LTA, Poly (I:C), and R-848], and anti-CD40 antibody (collectively abbreviated as rWTC-MBTA). We evaluated the therapeutic efficacy of rWTC-MBTA strategy in a mouse syngeneic GL261 orthotopic GBM tumor model. rWTC-MBTA or vehicle control were administered subcutaneously over the right foreleg three days after intracranial injection of GL261 cells. Complete regression (CR) of intracranial tumors was achieved in 70% (7/10) of rWTC-MBTA treated animals while none survived in the control group. Immunophenotyping analyses of peripheral lymph nodes and brain tumors of rWTC-MBTA treated mice demonstrated: (1) increased mature dendritic cells and MHC II+ monocytes; (2) increased effector (CD62L-CD44+) CD4-T and CD8-T cells; (3) increased cytotoxic IFNγ-, TNFα-, and granzyme B-secreting CD4-T and CD8-T cells. Of note, the therapeutic efficacy of rWTC-MBTA disappeared in CD4-T and/or CD8-T lymphocyte depleted mice. Three mice that achieved CR were rechallenged with 50k GL261 cells intracranially 14 months after the last rWTC-MBTA treatment and all rechallenged animals resisted GL261 tumor development, confirming the establishment of long-term immunological memory against GL261 tumor cells. Collectively, our study demonstrated that rWTC-MBTA strategy can effectively activate antigen presenting cells and induce more favorable T-cell signatures in the GBM tumors.

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Thermostable Vaccines: Past, Present and Future Perspectives

Pakistan BioMedical Journal ◽

10.52229/pbmj.v2i1.26 ◽

2019 ◽

Vol 2 (1) ◽

Author(s):

Misbah Farooqui ◽

Amir Sultan ◽

Hassan Ahmed Khan

Keyword(s):

Immune Response ◽

Adaptive Immune Response ◽

Vaccine Formulation ◽

Immunization Programs ◽

Future Perspectives ◽

Critical Part ◽

Adaptive Immune ◽

Development Cycle ◽

New Vaccines ◽

Thermostable Vaccine

Vaccines stability has a major role in the success of immunization programs and saves millions of livesevery year. To stabilize vaccines cold chains are developed for storage and transport, as efficiency ofvaccines is hampered if they are not kept under proper temperature. Aluminum is used for making vaccinethermostable. The development of vaccine formulation is a critical part of overall development cycle ofapproving, testing and producing new vaccines. However, Liquid vaccine formulation is still preferred overdry formulation because of ease in using, packaging and manufacturing. Other approaches have beenused to make vaccine thermostable. This study demonstrates those processes, used to develop thermosensitivevaccines into thermostable vaccine and also describes vaccine formulation designing and useof heat shock protein including mHSP70 and mHSP65 to generate innate and adaptive immune response.

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Photodynamic Therapy Using a New Folate Receptor-Targeted Photosensitizer on Peritoneal Ovarian Cancer Cells Induces the Release of Extracellular Vesicles with Immunoactivating Properties

Journal of Clinical Medicine ◽

10.3390/jcm9041185 ◽

2020 ◽

Vol 9 (4) ◽

pp. 1185 ◽

Cited By ~ 3

Author(s):

Martha Baydoun ◽

Olivier Moralès ◽

Céline Frochot ◽

Colombeau Ludovic ◽

Bertrand Leroux ◽

...

Keyword(s):

Ovarian Cancer ◽

Immune Response ◽

Photodynamic Therapy ◽

Cancer Cells ◽

Tumor Cells ◽

Extracellular Vesicles ◽

Immune Cells ◽

Surgical Techniques ◽

Ovarian Cancer Cells ◽

The Impact

Often discovered at an advanced stage, ovarian cancer progresses to peritoneal carcinoma, which corresponds to the invasion of the serosa by multiple tumor implants. The current treatment is based on the combination of chemotherapy and tumor cytoreduction surgery. Despite the progress and standardization of surgical techniques combined with effective chemotherapy, post-treatment recurrences affect more than 60% of women in remission. Photodynamic therapy (PDT) has been particularly indicated for the treatment of superficial lesions on large surfaces and appears to be a relevant candidate for the treatment of microscopic intraperitoneal lesions and non-visible lesions. However, the impact of this therapy on immune cells remains unclear. Hence, the objective of this study is to validate the efficacy of a new photosensitizer [pyropheophorbide a-polyethylene glycol-folic acid (PS)] on human ovarian cancer cells and to assess the impact of the secretome of PDT-treated cells on human peripheral blood mononuclear cells (PBMC). We show that PS, upon illumination, can induce cell death of different ovarian tumor cells. Furthermore, PDT using this new PS seems to favor activation of the immune response by inducing the secretion of effective cytokines and inhibiting the pro-inflammatory and immunosuppressive ones, as well as releasing extracellular vesicles (EVs) prone to activating immune cells. Finally, we show that PDT can activate CD4+ and CD8+ T cells, resulting in a potential immunostimulating process. The results of this pilot study therefore indicate that PS-PDT treatment may not only be effective in rapidly and directly destroying target tumor cells but also promote the activation of an effective immune response; notably, by EVs. These data thus open up good prospects for the treatment of micrometastases of intraperitoneal ovarian carcinosis which are currently inoperable.

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Salmonella engineered to express CD20-targeting antibodies and a drug-converting enzyme can eradicate human lymphomas

Blood ◽

10.1182/blood-2012-12-474098 ◽

2013 ◽

Vol 122 (5) ◽

pp. 705-714 ◽

Cited By ~ 37

Author(s):

Paul E. Massa ◽

Aida Paniccia ◽

Ana Monegal ◽

Ario de Marco ◽

Maria Rescigno

Keyword(s):

Immune Response ◽

Tumor Cells ◽

Tumor Antigen ◽

Adaptive Immune Response ◽

Human Tumors ◽

Converting Enzyme ◽

Adaptive Immune ◽

Key Points

Key PointsSalmonella is engineered to specifically infect tumor cells based on recognition of a tumor antigen by a bacterial-expressed antibody. Once inside, Salmonella can transfer cytotoxic cargos to destroy human tumors even in the absence of an adaptive immune response.

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Production of Adenosine by Ectonucleotidases: A Key Factor in Tumor Immunoescape

Journal of Biomedicine and Biotechnology ◽

10.1155/2012/473712 ◽

2012 ◽

Vol 2012 ◽

pp. 1-9 ◽

Cited By ~ 47

Author(s):

François Ghiringhelli ◽

Mélanie Bruchard ◽

Fanny Chalmin ◽

Cédric Rébé

Keyword(s):

Immune Response ◽

Cancer Cells ◽

Tumor Cells ◽

Stromal Cells ◽

T Cell Response ◽

Antitumor Immune Response ◽

Tumor Bed ◽

Wide Range ◽

Key Factor ◽

The Impact

It is now well known that tumor immunosurveillance contributes to the control of cancer growth. Many mechanisms can be used by cancer cells to avoid the antitumor immune response. One such mechanism relies on the capacity of cancer cells or more generally of the tumor microenvironment to generate adenosine, a major molecule involved in antitumor T cell response suppression. Adenosine is generated by the dephosphorylation of extracellular ATP released by dying tumor cells. The conversion of ATP into adenosine is mediated by ectonucleotidase molecules, namely, CD73 and CD39. These molecules are frequently expressed in the tumor bed by a wide range of cells including tumor cells, regulatory T cells, Th17 cells, myeloid cells, and stromal cells. Recent evidence suggests that targeting adenosine by inhibiting ectonucleotidases may restore the resident antitumor immune response or enhance the efficacy of antitumor therapies. This paper will underline the impact of adenosine and ectonucleotidases on the antitumor response.

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Immune Response to SARS-CoV-2 Infection

International Journal of Current Science Research and Review ◽

10.47191/ijcsrr/v3-i10-03 ◽

2020 ◽

Vol 03 (10) ◽

Author(s):

Dr. Ahmed Al-Shukaili ◽

Keyword(s):

Immune Response ◽

Immune System ◽

Severe Acute Respiratory Syndrome ◽

Global Health ◽

Immune Cells ◽

Current Knowledge ◽

Adaptive Immune ◽

Proinflammatory Mediators ◽

Adaptive Immune Cells ◽

New Type

In December 2019 a new type of coronaviruses appeared in China and named Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the disease associated with this virus is called Coronavirus Disease 2019 or COVID-19. Currently, COVID19 is the main global health threat. In this review, we focus in the current knowledge of immune response to SARS-CoV-2. Dysregulation of immune system, such as elevation levels of proinflammatory mediators and their roles in disease progression and pathogenesis as well as imbalance between innate and adaptive immune cells, are discussed in this review.

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Control of the Antitumor Immune Response by Cancer Metabolism

Cells ◽

10.3390/cells8020104 ◽

2019 ◽

Vol 8 (2) ◽

pp. 104 ◽

Cited By ~ 17

Author(s):

Charlotte Domblides ◽

Lydia Lartigue ◽

Benjamin Faustin

Keyword(s):

Immune Response ◽

Tumor Cells ◽

Cancer Metabolism ◽

Hematological Malignancies ◽

Immune Cell ◽

Immune Escape ◽

Positive Impact ◽

Metabolic Reprogramming ◽

Antitumor Immune Response ◽

Molecular Events

The metabolic reprogramming of tumor cells and immune escape are two major hallmarks of cancer cells. The metabolic changes that occur during tumorigenesis, enabling survival and proliferation, are described for both solid and hematological malignancies. Concurrently, tumor cells have deployed mechanisms to escape immune cell recognition and destruction. Additionally, therapeutic blocking of tumor-mediated immunosuppression has proven to have an unprecedented positive impact in clinical oncology. Increased evidence suggests that cancer metabolism not only plays a crucial role in cancer signaling for sustaining tumorigenesis and survival, but also has wider implications in the regulation of antitumor immune signaling through both the release of signaling molecules and the expression of immune membrane ligands. Here, we review these molecular events to highlight the contribution of cancer cell metabolic reprogramming on the shaping of the antitumor immune response.

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