The Tumor Immune Microenvironment and Frameshift Neoantigen Load Determine Response to PD-L1 Blockade in Extensive-Stage SCLC

Kanemura, Hiroaki; Hayashi, Hidetoshi; Tomida, Shuta; Tanizaki, Junko; Suzuki, Shinichiro; Kawanaka, Yusuke; Tsuya, Asuka; Fukuda, Yasushi; Kudo, Kazuhiko; Takahama, Takayuki; Imai, Ryosuke; Haratani, Koji; Chiba, Yasutaka; Otani, Tomoyuki; Ito, Akihiko; Sakai, Kazuko; Nishio, Kazuto; Nakagawa, Kazuhiko

doi:10.1016/j.jtocrr.2022.100373

Cited by 7 publications

(7 citation statements)

References 42 publications

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“…Scoring of CD44 and CD133 was performed according to the semiquantitative H-score, which was calculated by multiplying the cytomembrane staining intensity (0 = no staining, 1+ = weak staining, 2+ = moderate staining, 3+ = strong staining) by the percentage of stained cells (0% to 100%). 16 PD-L1 immunostaining was optimized with human placenta and tonsil as positive controls, and the percentage of tumor cells with membranous staining at any intensity was determined as the PD-L1 tumor proportion score (TPS), 17 , 18 with overall PD-L1 positivity being defined with a cutoff of greater than or equal to 1% of tumor cells (<1% defined as negative). TILs were evaluated on the basis of staining for CD8, with their number being determined at an absolute magnification of 400× (0.20 mm 2 per field).…”

Section: Methodsmentioning

confidence: 99%

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The Tumor Immune Microenvironment Is Associated With Recurrence in Early-Stage Lung Adenocarcinoma

Kanemura,

Yokoyama,

Nakajima

et al. 2024

JTO Clinical and Research Reports

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Section: Methodsmentioning

confidence: 99%

“…At least one and a maximum of five scanned fields of tumor regions were randomly chosen for each TIL count, and the TIL density in each tumor was calculated by dividing the number of TILs by the sum of the areas (mm 2 ) of the viewed fields. 18 TILs were defined as cells positive for CD8 at any staining intensity.…”

Section: Methodsmentioning

confidence: 99%

The Tumor Immune Microenvironment Is Associated With Recurrence in Early-Stage Lung Adenocarcinoma

Kanemura,

Yokoyama,

Nakajima

et al. 2024

JTO Clinical and Research Reports

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“…Therefore, measuring immune checkpoint expression levels in tumors may help identify patients who are more likely to respond to combination therapy with CD47 blockade and checkpoint inhibitors. (4) Tumor mutational burden (TMB): Tumors with a higher TMB may be more responsive to CD47-targeted therapy, as they may have a higher number of neoantigens that can be recognized by the immune system [49,92]. Therefore, measuring TMB in tumors may help identify patients who are more likely to respond to CD47 blockade.…”

Section: Cd47-targeted Therapies Including Antibody-based Therapies C...mentioning

confidence: 99%

Opportunities and challenges of CD47-targeted therapy in cancer immunotherapy

CHEN,

GUO,

2024

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Cancer immunotherapy has emerged as a promising strategy for the treatment of cancer, with the tumor microenvironment (TME) playing a pivotal role in modulating the immune response. CD47, a cell surface protein, has been identified as a crucial regulator of the TME and a potential therapeutic target for cancer therapy. However, the precise functions and implications of CD47 in the TME during immunotherapy for cancer patients remain incompletely understood. This comprehensive review aims to provide an overview of CD47's multifaced role in TME regulation and immune evasion, elucidating its impact on various types of immunotherapy outcomes, including checkpoint inhibitors and CAR T-cell therapy. Notably, CD47-targeted therapies offer a promising avenue for improving cancer treatment outcomes, especially when combined with other immunotherapeutic approaches. The review also discusses current and potential CD47-targeted therapies being explored for cancer treatment and delves into the associated challenges and opportunities inherent in targeting CD47. Despite the demonstrated effectiveness of CD47-targeted therapies, there are potential problems, including unintended effects on healthy cells, hematological toxicities, and the development if resistance. Consequently, further research efforts are warranted to fully understand the underlying mechanisms of resistance and to optimize CD47-targeted therapies through innovative combination approaches, ultimately improving cancer treatment outcomes. Overall, this comprehensive review highlights the significance of CD47 as a promising target for cancer immunotherapy and provides valuable insight into the challenges and opportunities in developing effective CD47-targeted therapies for cancer treatment.

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“… 40 Other innovative approaches include microbial-based immunotherapy and injectable nanocomposite hydrogels for tumor treatment. 41 , 42 , 55 Clinical trials are ongoing, with some focusing on combining chemotherapy with immune checkpoint inhibitors to induce immunogenic tumor cell death and enhance neoantigen presentation. Despite progress, challenges, such as patient variability, tumor cell evasion, and immune suppression, remain.…”

Section: Neoantigen “Traps” For Tumorsmentioning

confidence: 99%

Evolving Tumor Characteristics and Smart Nanodrugs for Tumor Immunotherapy

Sun,

Xie,

Liu

et al. 2024

IJN

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Typical physiological characteristics of tumors, such as weak acidity, low oxygen content, and upregulation of certain enzymes in the tumor microenvironment (TME), provide survival advantages when exposed to targeted attacks by drugs and responsive nanomedicines. Consequently, cancer treatment has significantly progressed in recent years. However, the evolution and adaptation of tumor characteristics still pose many challenges for current treatment methods. Therefore, efficient and precise cancer treatments require an understanding of the heterogeneity degree of various factors in cancer cells during tumor evolution to exploit the typical TME characteristics and manage the mutation process. The highly heterogeneous tumor and infiltrating stromal cells, immune cells, and extracellular components collectively form a unique TME, which plays a crucial role in tumor malignancy, including proliferation, invasion, metastasis, and immune escape. Therefore, the development of new treatment methods that can adapt to the evolutionary characteristics of tumors has become an intense focus in current cancer treatment research. This paper explores the latest understanding of cancer evolution, focusing on how tumors use new antigens to shape their “new faces”; how immune system cells, such as cytotoxic T cells, regulatory T cells, macrophages, and natural killer cells, help tumors become “invisible”, that is, immune escape; whether the diverse cancer-associated fibroblasts provide support and coordination for tumors; and whether it is possible to attack tumors in reverse. This paper discusses the limitations of targeted therapy driven by tumor evolution factors and explores future strategies and the potential of intelligent nanomedicines, including the systematic coordination of tumor evolution factors and adaptive methods, to meet this therapeutic challenge.

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The Tumor Immune Microenvironment and Frameshift Neoantigen Load Determine Response to PD-L1 Blockade in Extensive-Stage SCLC

Cited by 7 publications

References 42 publications

The Tumor Immune Microenvironment Is Associated With Recurrence in Early-Stage Lung Adenocarcinoma

The Tumor Immune Microenvironment Is Associated With Recurrence in Early-Stage Lung Adenocarcinoma

Opportunities and challenges of CD47-targeted therapy in cancer immunotherapy

Evolving Tumor Characteristics and Smart Nanodrugs for Tumor Immunotherapy

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