Compartmental immune responses and biomarker discordance after neoadjuvant chemoimmunotherapy in resectable non-small cell lung cancer
Abstract
Neoadjuvant chemoimmunotherapy can produce uneven responses across the primary tumour, regional lymph nodes, and occult systemic disease. Pathology, circulating tumour DNA (ctDNA), and imaging capture different consequences of this response, so their disagreement can contain clinically relevant biological information. This structured narrative review examines same-patient evidence in resectable non-small cell lung cancer and interprets discordance through anatomical compartment, sampling time, and local immune context. Paired tissue studies show distinct primary and nodal immune ecologies and response-associated lymphoid and myeloid programmes. Spatial clonality and unequal shedding shape the circulating signal, while inflammatory and reparative tissue changes can sustain imaging abnormalities after tumour regression. These observations inform four proposed principles for multidisciplinary interpretation. Separate primary and nodal reporting preserves compartment-specific response information. Presurgical ctDNA clearance indicates molecular response, not proof of tissue eradication. Confirmed postoperative molecular conversion provides a rationale for reassessing current disease status. For imaging conflicts that could alter curative-intent management, lesion-level review can identify when tissue confirmation would be feasible and decision-changing. A postoperative pathology–molecular residual disease matrix organises research questions while preserving nodal findings, unresolved lesions, and serial molecular trajectory. The immediate contribution is to identify which additional observation can resolve a consequential conflict; treatment adaptation then requires evidence that acting on the result benefits patients. Biomarker discordance is therefore an interpretive problem with biological content, rather than a reason to let the most favourable test define the entire response.
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BibTeX
@article{han2026compartmental,
title = {{Compartmental immune responses and biomarker discordance after neoadjuvant chemoimmunotherapy in resectable non-small cell lung cancer}},
author = {Songchen Han and Ying Ma and Zhenjun Li and Wenlong Chen and Zhihui Xue and Yunjiu Gou},
journal = {Frontiers in Immunology},
year = {2026},
month = nov,
doi = {10.3389/fimmu.2026.1998081},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1998081},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Compartmental immune responses and biomarker discordance after neoadjuvant chemoimmunotherapy in resectable non-small cell lung cancer
AU - Songchen Han
AU - Ying Ma
AU - Zhenjun Li
AU - Wenlong Chen
AU - Zhihui Xue
AU - Yunjiu Gou
PY - 2026
DA - 2026/11/05
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1998081
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1998081
AB - Neoadjuvant chemoimmunotherapy can produce uneven responses across the primary tumour, regional lymph nodes, and occult systemic disease. Pathology, circulating tumour DNA (ctDNA), and imaging capture different consequences of this response, so their disagreement can contain clinically relevant biological information. This structured narrative review examines same-patient evidence in resectable non-small cell lung cancer and interprets discordance through anatomical compartment, sampling time, and local immune context. Paired tissue studies show distinct primary and nodal immune ecologies and response-associated lymphoid and myeloid programmes. Spatial clonality and unequal shedding shape the circulating signal, while inflammatory and reparative tissue changes can sustain imaging abnormalities after tumour regression. These observations inform four proposed principles for multidisciplinary interpretation. Separate primary and nodal reporting preserves compartment-specific response information. Presurgical ctDNA clearance indicates molecular response, not proof of tissue eradication. Confirmed postoperative molecular conversion provides a rationale for reassessing current disease status. For imaging conflicts that could alter curative-intent management, lesion-level review can identify when tissue confirmation would be feasible and decision-changing. A postoperative pathology–molecular residual disease matrix organises research questions while preserving nodal findings, unresolved lesions, and serial molecular trajectory. The immediate contribution is to identify which additional observation can resolve a consequential conflict; treatment adaptation then requires evidence that acting on the result benefits patients. Biomarker discordance is therefore an interpretive problem with biological content, rather than a reason to let the most favourable test define the entire response.
SN - 1664-3224
ER -