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Molecular Insights into the Immune Contexture of Tumors

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Dear Colleagues,

The immune contexture—comprising the composition, localization, and functional state of immune cells in the tumor microenvironment—has become a key determinant of cancer progression, therapeutic response, and prognosis. Advances in single-cell and spatial omics are revealing the complexity of tumor–immune interactions at unprecedented resolution.

This Special Issue welcomes original research articles and reviews that explore the molecular mechanisms shaping immune responses within tumors, with emphasis on clinically relevant biomarkers, mechanisms of immune evasion, and novel therapeutic strategies.

Topics of interest include (but are not limited to) the following:

Spatial profiling of immune cells in tumors;
Mechanisms of immune escape and T cell dysfunction;
Tumor-associated macrophages and myeloid cell reprogramming;
Tertiary lymphoid structures and local immune architecture;
Neoantigen landscape and antigen presentation defects;
Cytokine and chemokine networks in the tumor microenvironment;
Biomarkers for immunotherapy response and resistance;
Integration of multi-omics in tumor immunology;
Translational models for immuno-oncology.

We look forward to receiving your contributions.

Prof. Dr. Leonardo Oliveira Reis
Dr. Guilherme Zweig Rocha
Guest Editors

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31 pages, 1163 KB

Open AccessReview

Overcoming Immunotherapy Resistance in Small-Cell Lung Cancer

by Matteo Canale, Fabrizia Suzzi, Alberto Verlicchi, Fabrizio Citarella, Angelo Delmonte and Paola Ulivi

Biology 2026, 15(4), 356; https://doi.org/10.3390/biology15040356 - 19 Feb 2026

Viewed by 887

Abstract

Small-cell lung cancer (SCLC) is the most lethal histologic subtype of lung cancer. It is characterized by rapid tumor growth and early metastatic dissemination, resulting in an extremely poor prognosis. The addition of immunotherapy to standard chemotherapy has led to a modest improvement in survival for patients with extensive-stage disease. However, the overall clinical benefit remains limited due to both primary and acquired resistance to immunotherapy. Indeed, the efficacy of immune checkpoint inhibitors is influenced by multiple factors, including tumor heterogeneity, an immunosuppressive tumor microenvironment, and intrinsic molecular characteristics of the disease. In recent years, active research has been conducted to identify and therapeutically overcome resistance mechanisms to immunotherapy, and accumulating suggestive evidence is lighting the way for new strategies for clinical management of patients with SCLC. In this review article, we summarize and discuss the substantial obstacle to immunotherapy clinical efficacy, with a particular emphasis on the published and ongoing clinical trials that investigated the potential strategies to overcome mechanisms of resistance to immunotherapy. Moreover, we report and discuss the new therapeutic approaches tested, especially the use of antibody–drug conjugates, bi-specific antibodies, adoptive cell therapies and combination strategies. Full article

(This article belongs to the Special Issue Molecular Insights into the Immune Contexture of Tumors)

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